Leukocyte Adhesion Inhibitor-1 (LAI-1)

Abstract

There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human chemokine beta-11 (Ck beta-11) polypeptide and a human leukocyte adhesion inhibitor-1 (LAI-1) polypeptide (previously termed chemokine α1 (CKα1 or cka-1), as well as Ck beta-11 and/or LAI-1 polypeptides themselves, as are vectors, host cells and recombinant methods for producing the same.

1 . An isolated leukocyte adhesion inhibitor-1 (LAI-1) polypeptide having an amino acid sequence selected from the group consisting of:
 (a) Val (23)-Pro (109) of SEQ ID NO:4;   (b) Val (26)-Pro (109) of SEQ ID NO:4;   (c) Thr (29)-Pro (109) of SEQ ID NO:4; and   (d) Ser (30)-Pro (109) of SEQ ID NO:4.   
     
     
         2 . The isolated polypeptide of  claim 1 , which is produced recombinantly using a baculovirus expression system. 
     
     
         3 . A method of inhibiting angiogenesis, comprising administering to an animal an effective amount of an LAI-1 polypeptide of  claim 1 . 
     
     
         4 . A method of inhibiting adhesion of peripheral blood mononuclear cells (PBMCs) to endothelial cells comprising administering to an animal an effective amount of the polypeptide of  claim 1 . 
     
     
         5 . The method of  claim 4 , wherein said inhibition alleviates or prevents joint inflammation. 
     
     
         6 . An isolated Chemokine β-11 polypeptide having an amino acid sequence of Gly (22)-Ser (98) of SEQ ID NO:2. 
     
     
         7 . A method for attracting T-lymphocytes comprising administering to an animal an effective amount of the polypeptide of  claim 6 . 
     
     
         8 . The isolated polypeptide of  claim 1 , wherein at position 30 of said amino acid sequence, Glu is substituted for Ser. 
     
     
         9 . An isolated antibody or fragment thereof that specifically binds to a protein selected from the group consisting of:
 (a) a protein whose amino acid sequence consists of amino acid residues 1 to 109 of SEQ ID NO:4;   (b) a protein whose amino acid sequence consists of amino acid residues 23 to 109 of SEQ ID NO:4;   (c) a protein whose amino acid sequence consists of a portion of SEQ ID NO:4, wherein said portion is at least 30 contiguous amino acid residues in length; and   (d) a protein whose amino acid sequence consists of a portion of SEQ ID NO:4, wherein said portion is at least 50 contiguous amino acid residues in length.   
     
     
         10 . An isolated polynucleotide comprising a member selected from the group consisting of:
 (a) a polynucleotide encoding the polypeptide as set forth in SEQ ID NO:2;   (b) a polynucleotide encoding the polypeptide as set forth in SEQ ID NO:4;   (c) a polynucleotide which encodes a mature polypeptide encoded by the DNA contained in ATCC Deposit No. 75948; and   (d) a polynucleotide which encodes a mature polypeptide encoded by the DNA contained in ATCC Deposit No. 75947.   
     
     
         11 . A vector containing the isolated polynucleotide of  claim 10 . 
     
     
         12 . The vector of  claim 11 , wherein the isolated polynucleotide is DNA. 
     
     
         13 . A host cell genetically engineered with the vector of  claim 12 . 
     
     
         14 . A host cell comprising the expression vector of  claim 13 . 
     
     
         15 . A process for producing a polypeptide comprising:
 (a) culturing the host cell of  claim 14  under conditions suitable for the expression of the polypeptide; and   (b) recovering said polypeptide from the cell culture.