Endothelial cell-leukocyte adhesion molecules (ELAMs) and molecules involved in leukocyte adhesion (MILAs)

Abstract

DNA sequences encoding endothelial cell-leukocyte adhesion molecules ELAMs, methods for producing such molecules, and ELAMs (including the specific molecules ELAM1 and VCAM1 and 1b) essentially free of normally associated animal proteins are disclosed. Antibodies against ELAMs are also disclosed. DNA sequences encoding molecules involved in leukocyte adhesion (MILAs), methods for producing such molecules and MILAs (including the specific molecule, CDX) essentially free of normally associated animal proteins are also disclosed. Antibody preparations which are reactive for MILAs and also disclosed. We disclose DNA sequences designated clone 7.2 and clone 1, which cause cells transformed with them to express 1,3-fucosyl transferases and which are involved in CDX expression. We also disclose protein 7.2 and protein 1 which are encoded by clone 7.2 and clone 1, respectively. We also disclose Pseudo-X and Pseudo-X 2 , proteins which cause COS cells and CHO cells to bind to ELAM1 and to be recognized by α-CDX antibodies. Methods for identifying molecules which inhibit binding of leukocytes to endothelial cells, methods for inhibiting leukocyte binding to endothelial cells, and methods for detecting acute inflammation are disclosed.

We claim:  
     
         1 . A DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof selected from the group consisting of: 
 (a) the ELAM1 DNA sequence of FIG. 1 from nucleotide number 141 to number 1970;    (b) the ELAM1 DNA sequence of FIG. 1 from nucleotide number 144 to number 1970;    (c) a DNA sequence encoding an amino acid sequence of a mature ELAMI;    (d) the DNA sequence of FIG. 1 from nucleotide number 204 to number 1970, optionally including an ATG start codon at its 5′ end;    (e) a DNA sequence encoding a soluble ELAM1;    (f) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions; and    (g) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences.    
     
     
         2 . A recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof, wherein said DNA sequence is selected from the group consisting of: 
 (a) the ELAM1 DNA sequence of FIG. 1 from nucleotide number 141 to number 1970;    (b) the ELAM1 DNA sequence of FIG. 1 from nucleotide number 144 to number 1970;    (c) a DNA sequence encoding an amino acid sequence of a mature ELAM1;    (d) the DNA sequence of FIG. 1 from nucleotide number 204 to number 1970, optionally including an ATG start codon at its 5′ end;    (e) a DNA sequence encoding a soluble ELAM1;    (f) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions; and    (g) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences.    
     
     
         3 . A recombinant DNA molecule according to  claim 2  wherein said DNA sequence is operatively linked to an expression control sequence.  
     
     
         4 . The recombinant DNA molecule of  claim 3 , wherein said expression control sequence is selected from the group consisting of the early or late promoters of SV40 or adenovirus, the lac system, the try system, the TAC system, the TRC system, the major operator and promoter regions of phage λ, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase, the promoters of acid phosphatase and the promoters of the yeast a-mating factors.  
     
     
         5 . A recombinant DNA molecule according to  claim 3  comprising plasmid ELAM pCDM8 clone 6.  
     
     
         6 . A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or fragment thereof, wherein said DNA sequence is selected from the group consisting of: 
 (a) the ELAM1 DNA sequence of FIG. 1 from nucleotide number 141 to number 1970;    (b) the ELAM1 DNA sequence of FIG. 1 from nucleotide number 144 to number 1970;    (c) a DNA sequence encoding an amino acid sequence of a mature ELAM1;    (d) the DNA sequence of FIG. 1 from nucleotide number 204 to number 1970 optionally containing an ATG start codon at its 5′ end;    (e) a DNA sequence encoding a soluble ELAM1;    (f) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions; and    (g) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences; wherein said DNA sequence is operatively linked to an expression control sequence.    
     
     
         7 . A unicellular host according to  claim 6 , wherein said expression control sequence is selected from the group consisting of the early or late promoters of SV40 or adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage,A, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase, the promoters of acid phosphatase and the promoters of the yeast a-mating factors.  
     
     
         8 . A transformed host according to  claim 6 , comprising plasmid ELAM pCDM8 clone 6.  
     
     
         9 . A transformed host according to  claim 6  wherein the unicellular host is selected from the group consisting of  E.coli , Pseudomonas, Bacillus, Streptomyces, yeasts, CHO, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, and BMT10 cells, plant cells, insect cells, and human cells in tissue culture.  
     
     
         10 . A method for producing ELAM1 comprising the step of culturing a transformed host according to  claim 7 .  
     
     
         11 . A cytokine-inducible expression control sequence derived from the nucleotide sequence of FIG. 7.  
     
     
         12 . The cytokine-inducible expression control sequence of  claim 11  comprising nucleotides 740-1307 of FIG. 7.  
     
     
         13 . An ELAM or fragment thereof essentially free of normally associated animal proteins selected from the group consisting of ELAM1, the lectin-like domain of ELAM1, the EGF-like domain of ELAM1, the consensus cysteine repeat unit of ELAM1, soluble ELAM1, mature ELAM1, and ELAM1 fragments capable of binding to an ELAM1 ligand.  
     
     
         14 . A molecule according to  claim 13  comprising the amino acid sequence of FIG. 1 from amino acid number 22 (Trp) to amino acid number 609 (Leu) optionally including an N-terminal methionine residue.  
     
     
         15 . Hybridoma CDB.BBll.BC6 anti-ELAM1.  
     
     
         16 . The monoclonal antibodies produced by hybridoma CDB.BB11.BC6 anti-ELAM1.  
     
     
         17 . A DNA sequence encoding a MILA for ELAM1 or fragment thereof.  
     
     
         18 . The DNA sequence according to  claim 17  wherein the MILA is CDX.  
     
     
         19 . The DNA sequence according to  claim 17  wherein the MILA is an ELAM1 ligand.  
     
     
         20 . A recombinant DNA molecule comprising a DNA sequence encoding a MILA for ELAM1 or a fragment thereof.  
     
     
         21 . The recombinant DNA molecule of  claim 20 , wherein the MILA is CDX.  
     
     
         22 . The recombinant DNA molecule of  claim 20 , wherein the MILA is an ELAM1 ligand.  
     
     
         23 . The recombinant DNA molecule of  claim 20  wherein said DNA sequence is operatively linked to an expression control sequence.  
     
     
         24 . A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding a MILA for ELAM1 or fragment thereof.  
     
     
         25 . The unicellular host of  claim 24 , wherein the MILA is CDX.  
     
     
         26 . The unicellular host of  claim 24 , wherein the MILA is an ELAM1 ligand.  
     
     
         27 . A unicellular host of  claim 24  selected from the group consisting of  E.coli , Pseudomonas, Bacillus, Streptomyces, yeasts, CHO, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, BMT10, insect cells, plant cells, and human cells in tissue culture.  
     
     
         28 . A MILA for ELAMI or a fragment thereof, substantially free of normally associated animal proteins.  
     
     
         29 . The MILA of  claim 28  comprising CDX.  
     
     
         30 . The MILA according to  claim 28  comprising an ELAM1 ligand.  
     
     
         31 . A fragment of a MILA according to  claim 28  that binds to ELAM1.  
     
     
         32 . The MILA fragment according to  claim 31 , wherein said fragment is a carbohydrate.  
     
     
         33 . Hybridoma SGB 3 B 4 .  
     
     
         34 . The monoclonal antibodies produced by hybridoma SGB 3 B 4 .  
     
     
         35 . An antibody preparation that is reactive to a MILA for ELAM1 but non-reactive to other proteins on the leukocyte cell surface.  
     
     
         36 . The antibody preparation of  claim 35  wherein the MILA is CDX.  
     
     
         37 . The antibody preparation of  claim 35  consisting essentially of monoclonal antibodies.  
     
     
         38 . A method for producing an antibody preparation reactive to a MILA for ELAM1 comprising the step of immunizing an organism with CDX or an antigenic fragment thereof.  
     
     
         39 . A DNA sequence encoding an endothelial cell-leukocyte adhesion molecule or fragment thereof selected from the group consisting of 
 (a) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 107 to number 2047;    (b) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 110 to number 2047;    (c) a DNA sequence encoding an amino acid sequence of a mature VCAM1;    (d) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 179 to 2047, optionally including an ATG start-codon at its 5′ end;    (e) a DNA sequence encoding a soluble VCAM1;    (f) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 100 to number 2316;    (g) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 103 to number 2316;    (h) a DNA sequence encoding an amino acid sequence of mature VCAM1b;    (i) a DNA sequence encoding a soluble VCAM1b;    (j) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 172 to 2316, optionally including an ATG start codon at its 5′ end;    (k) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions; and    (l) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences.    
     
     
         40 . A recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof wherein said DNA sequence is selected from the group consisting of: 
 (a) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 107 to number 2047;    (b) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 110 to number 2047;    (c) a DNA sequence encoding an amino acid sequence of mature VCAM1;    (d) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 172 to 2316, optionally including an ATG start codon at its 5′ end;    (e) a DNA sequence encoding a soluble VCAM1;    (f) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 100 to number 2316;    (g) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 103 to number 2316;    (h) a DNA sequence encoding an amino acid sequence of mature VCAM1b;    (i) a DNA sequence encoding a soluble VCAM1b;    (j) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 172 to 2316, optionally including an ATG start codon at its 5′ end;    (k) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions; and    (l) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences.    
     
     
         41 . The recombinant DNA molecule of  claim 40  wherein said DNA sequence is operatively linked to an expression control sequence.  
     
     
         42 . The recombinant DNA molecule of  claim 41 , wherein said expression control sequence is selected from the group consisting of the early or late promoters of SV40 or adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage λ, the control regions of fd coat protein, the promoter of 3-phosphoglycerate kinase, the promoters of acid phosphatase and the promoters of yeast a-mating factors.  
     
     
         43 . A recombinant DNA molecule according to  claim 41 , comprising plasmid AM pCDM 8 clone 41 or plasmid VCAM 1B clone lEll pCDM8.  
     
     
         44 . A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof, wherein said DNA sequence is selected from the group consisting of: 
 (a) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 107 to number 2047;    (b) the VCAM1 DNA sequence of FIG. 3 from nucleotide number 110 to number 2047;    (c) a DNA sequence encoding an amino acid sequence of mature VCAM1;    (d) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 172 to 2316, optionally including an ATG start codon at its 5′ end;    (e) a DNA sequence encoding a soluble VCAM1;    (f) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 100 to number 2316;    (g) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 103 to number 2316;    (h) a DNA sequence encoding an amino acid sequence of mature VCAM1b;    (i) a DNA sequence encoding a soluble VCAM1b;    (j) the VCAM1b DNA sequence of FIG. 4 from nucleotide number 172 to 2316, optionally including an ATG start codon at its 5′ end;    (k) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions; and    (l) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences; and wherein said DNA sequence is operatively linked to an expression control sequence.    
     
     
         45 . A unicellular host according to  claim 44 , wherein the recombinant DNA molecule comprises plasmid AM pCDM 8 clone 41 or clone VCAM 1B pCDM8 clone 1E11.  
     
     
         46 . A unicellular host of  claim 44 , selected from the group consisting of  E.coli , Pseudomonas, Bacillus, Streptomyces, yeasts, CHO, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, and BMT10, insect cells, plant cells, and human cells in tissue culture.  
     
     
         47 . A method for producing VCAM1 comprising the step of culturing a unicellular host according to  claim 44 .  
     
     
         48 . VCAM1 or VCAM1b or a fragment thereof essentially free of normally associated animal proteins.  
     
     
         49 . A VCAM1 or VCAM1b polypeptide selected from the group consisting of domain 1 of VCAM1, domain 2 of VCAM1, domain 3 of VCAM1, domain 4 of VCAM1, domain 5 of VCAM1, domain 6 of VCAM1, domain 3 of VCAM1b, domain 3B of VCAM1b, domain 4 of VCAM1b, and combinations thereof.  
     
     
         50 . A VCAM1 according to  claim 48 , comprising the amino acid sequence of FIG. 3 from amino acid number 25 to amino acid number 647, optionally including an N-terminal methionine residue.  
     
     
         51 . An antibody preparation that is reactive for VCAM1 or VCAM1b but non-reactive for other adhesion molecules expressed on the endothelial cell surface.  
     
     
         52 . The antibody preparation of  claim 51  wherein said antibody preparation consists essentially of monoclonal antibodies.  
     
     
         53 . A hybridoma producing monoclonal antibodies that recognize VCAM1.  
     
     
         54 . A method for producing antibodies which recognize VCAM1 or VCAM1b, comprising the step of immunizing an organism with VCAM1 or VCAM1b or an antigenic fragment thereof.  
     
     
         55 . A method for identifying molecules which inhibit binding of leukocytes to endothelial cells comprising the steps of: 
 (a) contacting a molecule with an ELAM or with ELAM-expressing cells to create a first mixture;    (b) contacting said first mixture with an ELAM ligand or with cells expressing a MILA or another molecule that binds to an ELAM, to create a second mixture; and    (c) testing said second mixture for the amount of said ELAM or ELAM expressing cells bound to said ELAM ligand or cells expressing a MILA or another molecule that binds to an ELAM.    
     
     
         56 . A method for identifying molecules which inhibit binding of leukocytes to endothelial cells comprising the steps of: 
 (a) contacting a molecule with an ELAM ligand or with cells expressing a MILA or a molecule that binds to an ELAM, to create a first mixture;    (b) contacting said first mixture with an ELAM or with ELAM expressing cells to create a second mixture; and    (c) testing said second mixture for the amount of said ELAM ligand or cells expressing a MILA or a molecule that binds to an ELAM, bound to said ELAM or ELAM-expressing cells.    
     
     
         57 . The method of  claim 55  or  56 , wherein and the ELAM is ELAM1.  
     
     
         58 . The method of  claim 55  or  56 , wherein the ELAM ligand is ELAM1 ligand.  
     
     
         59 . The method of  claim 55  or  56 , wherein the cells express a molecule selected from the group consisting of CDX, Pseudo-X and Pseudo-X 2 .  
     
     
         60 . The method of  claim 55  or  56 , wherein the ELAM is VCAM1 or VCAM1b.  
     
     
         61 . The method of  claim 55  or  56 , wherein the MILA is a VCAM1 or VCAM1b ligand.  
     
     
         62 . The method of  claim 55  or  56  wherein the MILA is VLA4.  
     
     
         63 . A method of inhibiting adhesion between leukocytes and endothelial cells in a system containing them comprising the step of introducing an effective amount of an inhibitory agent into said system, wherein said inhibitory agent is selected from the group consisting of ELAMs or fragments thereof capable of binding to ELAM ligands, antibodies recognizing MILAs, ELAM ligands or fragments thereof capable binding to ELAMs, carbohydrates binding to ELAMS, and antibodies recognizing ELAMs.  
     
     
         64 . The method of  claim 63 , wherein the inhibitory agent is ELAM1 or a fragment of an ELAM selected from the group consisting of the lectin-like domain of an ELAM1, the EGF-like domain of ELAM1, the consensus cysteine repeat of ELAM1, and a soluble ELAM1.  
     
     
         65 . The method of  claim 63 , wherein the inhibitory agent is a preparation of monoclonal antibodies recognizing ELAM1 ligand.  
     
     
         66 . The method of  claim 63 , wherein the inhibitory agent is a monoclonal antibody which recognizes CDX.  
     
     
         67 . The method of  claim 66 , wherein the monoclonal antibody is that produced by hybridoma SGB 3 B 4 .  
     
     
         68 . The method of  claim 63 , wherein said inhibitory agent is an ELAM1 ligand or a fragment thereof capable of binding to ELAM1.  
     
     
         69 . The method of  claim 63 , wherein the inhibitory agent is a monoclonal antibody recognizing ELAMI.  
     
     
         70 . The method of  claim 69  wherein the monoclonal antibody is that produced by hybridoma CDB.BBll.BC6 anti-ELAM1.  
     
     
         71 . The method of  claim 63  wherein said inhibitory agent is selected from the group consisting of VCAM1, VCAM1b and fragments thereof that bind to VLA4.  
     
     
         72 . The method of  claim 63  wherein said inhibitory agent is a.monoclonal antibody which recognizes a VCAMl ligand.  
     
     
         73 . The method of  claim 63  wherein said inhibitory agent is a VCAMl ligand or a fragment thereof that binds to VCAM1 or VCAM1b.  
     
     
         74 . The method of  claim 73  wherein the VCAMl ligand is VLA4.  
     
     
         75 . The method of  claim 63 , wherein said inhibitory agent is a monoclonal antibody that recognizes VCAM1 or VCAM1b.  
     
     
         76 . A method of detecting inflammation comprising the step of administering a detectably labelled compound selected from the group consisting of ELAM ligands, ELAM-binding fragments of an ELAM ligand, and antibodies which recognize an ELAM.  
     
     
         77 . A method of detecting inflammation comprising the steps of: 
 (a) contacting a sample of blood, serum, or other bodily fluid with detectably labelled ELAM ligands, ELAM-binding fragments of an ELAM ligand, or antibodies which recognize an ELAM, to create a mixture, and    (b) testing said mixture for the amount of ELAM ligand, ELAM-binding fragment of an ELAM ligand, or antibodies bound to an ELAM.    
     
     
         78 . The method of claims  76  or  77 , wherein the ELAM ligand is ELAM1 ligand.  
     
     
         79 . The method of claims  76  or  77  wherein the ELAM ligand is a VCAM1 ligand or VCAM1b ligand.  
     
     
         80 . The method of  claim 79  wherein the VCAM1 ligand is VLA4.  
     
     
         81 . The method of claims  76  or  77  wherein the antibodies are those produced by hybridoma CDB.B11.BC6 anti-ELAM1.  
     
     
         82 . A recombinant DNA molecule coding on expression for an ELAM/immunoglobulin fusion protein comprising a DNA sequence coding on expression for an ELAM or fragment thereof and a DNA sequence coding on expression for the constant region of an immunoglobulin molecule.  
     
     
         83 . The DNA sequence of  claim 82  wherein the ELAM is ELAM1, VCAM1 or VCAM1b.  
     
     
         84 . A recombinant DNA molecule according to  claim 82  comprising VCAM1 domains 1-3 and the constant regions of human immunoglobulin C-gamma-1.  
     
     
         85 . An antisense nucleic acid against an ELAM or MILA mRNA comprising a nucleic acid sequence hybridizing to said mRNA.  
     
     
         86 . The antisense oligonucleotide of  claim 85  which binds to the initiation codon of any of said mRNAs.  
     
     
         87 . The antisense nucleic acid of  claim 85  wherein the ELAM is ELAM1, VCAM1 or VCAM1b.  
     
     
         88 . The antisense nucleic acid of  claim 85 , wherein the MILA is an ELAM1 ligand.  
     
     
         89 . The antisense nucleic acid of  claim 85 , wherein the MILA is CDX.  
     
     
         90 . The antisense nucleic acid of  claim 85 , wherein the MILA is VLA4.  
     
     
         91 . The antisense nucleic acid of  claim 85  comprising DNA.  
     
     
         92 . An antisense nucleic acid of  claim 85 , comprising RNA.  
     
     
         93 . The antisense nucleic acid of  claim 85  having the DNA sequence 5′ CCC AGG CAT TTT AAG.  
     
     
         94 . A recombinant DNA molecule having a DNA sequence which, on transcription, produces an antisense ribonucleic acid against an ELAM or MILA mRNA, said antisense ribonucleic acid comprising a nucleic acid sequence hybridizing to said mRNA.  
     
     
         95 . An ELAM-producing or MILA-producing cell line transfected with a recombinant DNA molecule having a DNA sequence which, on transcription, produces an antisense ribonucleic acid against an ELAM or MILA mRNA, said antisense ribonucleic acid comprising a nucleic acid sequence hybridizing to said mRNA.  
     
     
         96 . A method for creating a cell line which exhibits reduced expression of an ELAM or MILA comprising transfecting an ELAM-producing or MILA-producing cell line with a recombinant DNA molecule having a DNA sequence which, upon transcription, produces an antisense ribonucleic acid against an ELAM or MILA mRNA, said antisense ribonucleic acid comprising a nucleic acid sequence hybridizing said mRNA.  
     
     
         97 . A method of treating inflammation comprising the step of administering an amount of an antisense nucleic acid according to  claim 82  effective to reduce production of one or more ELAMs or MILAs.  
     
     
         98 . A ribozyme which cleaves an ELAM or MILA mRNA.  
     
     
         99 . A ribozyme according to  claim 98  that cleaves ELAM1, VCAM1 or VCAM1b mRNA.  
     
     
         100 . A ribozyme according to  claim 98  that cleaves an ELAM ligand mRNA.  
     
     
         101 . A ribozyme according to  claim 98  that cleaves CDX mRNA.  
     
     
         102 . A ribozyme according to  claim 98  that cleaves VLA4 mRNA.  
     
     
         103 . A ribozyme according to  claim 98  further comprising a Tetrahvmena-type ribozyme.  
     
     
         104 . A ribozyme according to  claim 98  further comprising a hammerhead-type ribozyme.  
     
     
         105 . A recombinant DNA molecule comprising a DNA sequence which, upon transcription, produces a ribozyme that cleaves an ELAM or MILA mRNA.  
     
     
         106 . The ribozyme according to  claim 98  comprising the RNA sequence 5′ AAGGAUCACC UGAUGAGUCC GUGAGGACGA AACCAUCUU.  
     
     
         107 . An ELAM-producing or MILA-producing cell line transfected with a recombinant DNA molecule comprising a DNA sequence which, upon transcription, produces a ribozyme that cleaves an ELAM or MILA mRNA.  
     
     
         108 . A method for creating a cell line which exhibits reduced expression of an ELAM or MILA comprising transfecting an ELAM-producing or MILA-producing cell line with a recombinant DNA molecule that produces on transcription a ribozyme that cleaves an ELAM or MILA mRNA.  
     
     
         109 . A method of treating inflammation comprising the step of administering an amount of a ribozyme that cleaves an ELAM mRNA or an ELAM ligand mRNA effective to reduce the production of ELAM or ELAM ligand.  
     
     
         110 . An anti-idiotypic antibody preparation reactive to an ELAM or MILA.  
     
     
         111 . An anti-idiotypic antibody preparation of  claim 110  reactive to ELAM1, VCAM1 or VCAM1b.  
     
     
         112 . An anti-idiotypic antibody preparation of  claim 110  reactive to an ELAM1 ligand.  
     
     
         113 . An anti-idiotypic antibody preparation of  claim 110  reactive to VLA4.  
     
     
         114 . An anti-idiotypic antibody preparation of  claim 110  reactive to CDX.  
     
     
         115 . An anti-idiotypic antibody preparation of  claim 110  reactive to domains 1, 2, 3, 4, 5 or 6 of VCAM1 or domains 3, 3B or 4 of VCAM1b.  
     
     
         116 . A method for identifying an ELAM or ELAM-ligand which binds to any one of ELAM1, CDX, VCAM1, VCAM1b, or VLA4, comprising the steps of: 
 (a) screening a mixture of proteins for proteins that bind to anti-idiotypic antibodies recognizing antibodies that recognize any one of ELAM1, CDX, VCAM1, VCAM1b, or VLA4;    (b) isolating those molecules which bind to said anti-idiotypic antibodies; and    (c) testing the ability of those proteins to bind to ELAM1, CDX, VCAM1, VCAM1b, or VLA4.    
     
     
         117 . A method for identifying ELAM ligands which bind to any of the domains of VCAM1 or VCAM1b comprising the steps of: 
 (a) screening a mixture of proteins for proteins that bind to anti-idiotypic antibodies recognizing antibodies which recognize any of said domains of VCAM1 or VCAM1b;    (b) isolating those proteins that bind to said anti-idiotypic antibodies; and    (c) testing the ability of those proteins to bind to any of said domains of VCAM1 or VCAM1b.    
     
     
         118 . A method for inhibiting VCAM1 or VCAM1b expression comprising the step of administering an effective dose of an antibody which recognizes IL-1, TNF, or IFN-γ.  
     
     
         119 . A radioimmunoconjugate comprising an antibody conjugated to a nuclide, said antibody selected from the group consisting of antibodies recognizing VCAM1, antibodies recognizing VCAM1b, monoclonal antibody SGB 3 B 4  and monoclonal antibody BB11.  
     
     
         120 . The radioimmunoconjugate of  claim 119  wherein the nuclide is selected from the group consisting of  125 I,  90 Y, and  186 Re.  
     
     
         121 . An immunotoxin comprising an antibody recognizing VCAM1 or VCAM1b conjugated to a cell toxin.  
     
     
         122 . The immunotoxin of  claim 121  wherein the cell toxin is Pseudomonas exotoxin.  
     
     
         123 . A method for detecting VCAM1 or VCAM1b-producing cancer cells comprising the step of administering a radioimmunoconjugate having an antibody which recognizes VCAM1 or VCAM1b.  
     
     
         124 . A method for treating cancer comprising the step of administering an effective dose of a radioimmunoconjugate or immunotoxin having an antibody which recognizes VCAM1 or VCAM1b.  
     
     
         125 . A DNA sequence encoding a VCAM/ICAM fusion protein comprising DNA sequences for VCAM1 or VCAM1b domains binding a VCAM1 ligand and ICAM1 domains binding an ICAM1 ligand.  
     
     
         126 . A DNA sequence according to  claim 125  wherein the VCAM1 ligand is VLA4 and the ICAM1 ligand is LFA1.  
     
     
         127 . A VCAM/ICAM fusion protein comprising VCAM1 or VCAM1b domains binding a VCAM1 ligand and ICAM1 domains binding an ICAM1 ligand.  
     
     
         128 . A fusion protein according to  claim 127  wherein the VCAM1 ligand is VLA4 and the ICAM1 ligand is LFA1.  
     
     
         129 . A method for treating tumors expressing ELAM1, VCAM1, VCAM1b or a ligand thereof comprising: 
 (1) removing a sample of tumor tissue from a mammal having such a tumor,    (2) isolating from said sample one or more leukocytes that have infiltrated the tumor tissue,    (3) transfecting said one or more infiltrating leukocytes with a recombinant expression vector including a gene coding for a tumorcidal agent and capable of expressing in said leukocytes a tumorcidal gene product,    (4) introducing the transfected leukocytes into said mammal.    
     
     
         130 . A method according to  claim 129 , wherein the tumorcidal gene product is TNF or lymphotoxin.  
     
     
         131 . A method according to  claim 130 , wherein the mammal is a human.  
     
     
         132 . A method according to  claim 129 , wherein the recombinant expression vector is a retroviral vector.  
     
     
         133 . A method according to  claim 129 , wherein, prior to introduction of the transfected leukocytes into the mammal, said transfected leukocytes are expanded with IL-2.  
     
     
         134 . A method according to  claim 129 , wherein the tumor is a malignant tumor.  
     
     
         135 . A method according to  claim 129 , wherein the tumor expresses VLA4 or CDX.  
     
     
         136 . A method according to  claim 135 , wherein the tumor is melanoma or colon carcinoma.  
     
     
         137 . A method for enhancing the cytolytic properties of leukocytes against target cells expressing ELAMs or MILAs comprising transfecting said leukocytes with a recombinant expression vector including a gene coding for an ELAM or MILA molecule that binds to the ELAM or MILA expressed by said target cells, which recombinant expression vector is capable of expressing said gene in said leukocyte.  
     
     
         138 . A method according to 137, wherein the target cell is a melanoma or a colon carcinoma.  
     
     
         139 . A method according to  claim 138 , wherein the gene encodes VCAMl or VCAM1b, or encodes ELAMI.  
     
     
         140 . A method according to  claim 137 , wherein the recombinant expression vector is a retroviral vector.  
     
     
         141 . A method according to  claim 140 , wherein the recombinant expression vector also includes a gene encoding a tumorcidal agent.  
     
     
         142 . A method according to  claim 140 , wherein the leukocytes are tumor infiltrating leukocytes.  
     
     
         143 . A DNA sequence selected from the group consisting of: 
 (a) the DNA sequence of FIG. 9 from nucleotide 66 to 1280;    (b) the DNA sequence of FIG. 9 from nucleotide 69 to 1280;    (c) the DNA sequence of FIG. 10 from nucleotide 172 to 1761;    (d) the DNA sequence of FIG. 10 from nucleotide 175 to 1761;    (e) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions and have the biological activity of protein 7.2 or protein 1; and    (f) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences.    
     
     
         144 . A recombinant DNA molecule comprising a DNA sequence selected from the group consisting of: 
 (a) the DNA sequence of FIG. 9 from nucleotide 66 to 1280;    (b) the DNA sequence of FIG. 9 from nucleotide 69 to 1280;    (c) the DNA sequence of FIG. 10 from nucleotide 172 to 1761;    (d) the DNA sequence of FIG. 10 from nucleotide 175 to 1761;    (e) DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions and have the biological activity of protein 7.2 or protein 1; and    (f) DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences.    
     
     
         145 . The recombinant DNA molecule according to  claim 144  wherein said DNA sequence is operatively linked to an expression control sequence.  
     
     
         146 . A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding an amino acid sequence of FIG. 9 or FIG. 10.  
     
     
         147 . A unicellular host of  claim 146  selected from the group consisting of  E.coli , Pseudomonas, Bacillus, Streptomyces, yeasts, CHO, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, BMTlO, insect cells, plant cells, and human cells in tissue culture.  
     
     
         148 . A protein produced by the method of expressing in a unicellular host a recombinant DNA molecule according to  claim 144 .  
     
     
         149 . A process for producing a molecule that binds to ELAM1 comprising the step of expressing a DNA sequence encoding the amino acid sequence of FIG. 9 or FIG. 10 in a eukaryotic host cell.  
     
     
         150 . A process for producing a cell that adheres to ELAM1 comprising the step of expressing a DNA sequence encoding the amino acid sequence of FIG. 9 or FIG. 10 in a eukaryotic host cell.  
     
     
         151 . Pseudo-X or a fragment thereof capable of binding to α-CDX.  
     
     
         152 . Pseudo-X 2  or a fragment thereof capable of binding to α-CDX.  
     
     
         153 . A molecule capable of binding to ELAM1 comprising the carbohydrate moiety of a protein or a fucose-containing portion thereof wherein the protein is selected from the group consisting of CDX, Pseudo-X or Pseudo-X 2 .  
     
     
         154 . A molecule according to  claim 153  wherein the protein is CDX.  
     
     
         155 . A method of inhibiting adhesion between leukocytes and endothelial cells in a system containing them comprising the step of introducing in said system an effective amount of a molecule capable of binding to ELAM1, which molecule comprises a carbohydrate moiety of a protein or a fucose-containing portion thereof, wherein the protein is selected from the group consisting of CDX, Pseudo-X and Pseudo-X 2 .  
     
     
         156 . The method according to  claim 155  wherein the protein is CDX.  
     
     
         157 . A small molecule that inhibits the activity of the 1,3-fucosyl transferases described herein.  
     
     
         158 . A method of identifying small molecules that inhibit the activity of the 1,3-fucosyl transferases described herein comprising the steps of: 
 (1) contacting together an inhibitor candidate, a fucose acceptor and a 1,3-fucosyl transferase to create a test mixture and    (2) assaying the test mixture for 1,3-fucosyl transferase activity.    
     
     
         159 . The method according to  claim 158  wherein the fucose acceptor is LacNAc.  
     
     
         160 . The method according to  claim 158  wherein the fucose acceptor 2′-fucosyllactose.  
     
     
         161 . The method according to  claim 158  wherein the 1,3-fucosyl transferase is derived from an extract from a cell transformed with clone 7.2 or clone 1.  
     
     
         162 . The use of a 1,3-fucosyl transferase in a process for synthesizing an organic compound.  
     
     
         163 . A method of producing a 1,3 glycosidic bond between fucose and a fucose acceptor comprising the step of catalysis with a 1,3-fucosyl transferase as described herein.  
     
     
         164 . The method according to  claim 163  in which the fucose acceptor is a carbohydrate.  
     
     
         165 . Protein 7.2, protein 1, non-human homologues of protein 7.2 or protein 1 and biologically active fragments of any of the foregoing proteins.  
     
     
         166 . A cytokine-inducible expression control sequence derived from the nucleotide sequence of FIG. 8.  
     
     
         167 . The cytokine-inducible expression control sequence of  claim 166  comprising nucleotides 210-408 of FIG. 8.  
     
     
         168 . A ribozyme according to  claim 98  that cleaves mRNA for clone 7.2 or clone 1.