Human Chemokines CKBeta-4 and CKBeta-10/MCP-4

Abstract

Human chemokine polypeptides and DNA (RNA) encoding such chemokine polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such chemokine polypeptides for the treatment of leukemia, tumors, chronic infections, autoimmune disease, fibrotic disorders, wound healing and psoriasis. Antagonists against such chemokine polypeptides and their use as a therapeutic to treat rheumatoid arthritis, autoimmune and chronic inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever and bone marrow failure are also disclosed.

1 . An isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide encoding a Ckβ-4 polypeptide having the deduced amino acid sequence of SEQ ID NO. 2 or a fragment, analog or derivative of said polypeptide;    (b) a polynucleotide encoding a Ckβ-4 polypeptide having the amino acid sequence encoded by the cDNA contained in ATCC Deposit No. 75848 or a fragment, analog or derivative of said polypeptide.    (c) a polynucleotide encoding an MCP-4 polypeptide comprising in sequence amino acid residues 28-93 of the MCP-4 polypeptide of SEQ ID NO. 3 having the deduced amino acid sequence of SEQ ID NO. 4 or a fragment, analog or derivative of said polypeptide; and    (d) a polynucleotide encoding an MCP-4 polypeptide having an amino acid sequence encoded by the cDNA contained in ATCC Deposit No. 75849 or a fragment, analog or derivative of said polypeptide.    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 1  wherein the polynucleotide is genomic DNA.  
     
     
         5 . The polynucleotide of  claim 2  wherein said polynucleotide encodes Ckβ-4 having the deduced amino acid sequence of SEQ ID NO. 2.  
     
     
         6 . The polynucleotide of  claim 2  wherein said polynucleotide encodes MCP-4 having an amino acid sequence selected from the group consisting of residues 1-98, 17-98, 20-98, 22-98, 24-98, 28-98, 28-95 and 28-93 set out in SEQ ID NO. 4.  
     
     
         7 . The polynucleotide of  claim 2  wherein said polynucleotide encodes a Ckβ-4 polypeptide encoded by the cDNA of ATCC Deposit No. 75848.  
     
     
         8 . The polynucleotide of  claim 2  wherein said polynucleotide encodes an MCP-4 polypeptide encoded by the cDNA of ATCC Deposit No. 75849.  
     
     
         9 . The polynucleotide of  claim 1  having the coding sequence of Ckβ-4 as shown in SEQ ID NO. 1.  
     
     
         10 . The polynucleotide of  claim 1  having the coding sequence of MCP-4 as shown in SEQ ID NO. 3.  
     
     
         11 . The polynucleotide of  claim 2  having the coding sequence of Ckβ-4 deposited as ATCC Deposit No. 75848.  
     
     
         12 . The polynucleotide of  claim 2  having the coding sequence of MCP-4 deposited as ATCC Deposit No. 75849.  
     
     
         13 . A vector containing the DNA of  claim 2 .  
     
     
         14 . A host cell genetically engineered with the vector of  claim 13 .  
     
     
         15 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 14  the polypeptide encoded by said DNA.  
     
     
         16 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 13 .  
     
     
         17 . An isolated DNA hybridizable to the DNA of  claim 2  and encoding a polypeptide having Ckβ-4 activity.  
     
     
         18 . An isolated DNA hybridizable to the DNA of  claim 2  and encoding a polypeptide having MCP-4 activity.  
     
     
         19 . A polypeptide selected from the group consisting of (i) a Ckβ-4 polypeptide having the deduced amino acid sequence of SEQ ID NO. 2 and fragments, analogs and derivatives thereof (ii) a Ckβ-4 polypeptide encoded by the cDNA of ATCC Deposit No. 75848 and fragments, analogs and derivatives of said polypeptide (iii) an MCP-4 polypeptide having an amino acid sequence selected from the group consisting of residues 1-98, 17-98, 20-98, 22-98, 24-98, 28-98, 28-95 and 28-93 set of SEQ ID NO. 4 and fragments, analogs and derivatives thereof; and (iv) an MCP-4 polypeptide encoded by the cDNA of ATCC Deposit No. 75849 and fragments, analogs and derivatives of said polypeptide.  
     
     
         20 . The polypeptide of  claim 19  wherein the polypeptide is Ckβ-4 having the deduced amino acid sequence of SEQ ID NO. 2.  
     
     
         21 . The polypeptide of  claim 19  wherein the polypeptide is an MCP-4 polypeptide selected from the group set out in (iii).  
     
     
         22 . Antibodies against the polypeptides of  claim 19 .  
     
     
         23 . Antagonists against the polypeptides of  claim 19 .  
     
     
         24 . A method for the treatment of a patient having need of Ckβ-4 comprising: administering to the patient a therapeutically effective amount of the a Ckβ-4 polypeptide of  claim 19 .  
     
     
         25 . A method for the treatment of a patient having need to inhibit Ckβ-4 comprising: administering to the patient a therapeutically effective amount of a Ckβ-4 antagonist of  claim 23 .  
     
     
         26 . A method for the treatment of a patient having need of MCP-4 comprising: administering to the patient a therapeutically effective amount of an MCP-4 polypeptide of  claim 19 .  
     
     
         27 . A method for the treatment of a patient having need to inhibit MCP-4 comprising: administering to the patient a therapeutically effective amount of the antagonist of  claim 23 .  
     
     
         28 . A composition comprising a polypeptide of  claim 19  and an acceptable carrier.  
     
     
         29 . The method of  claim 24  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         30 . The method of  claim 26  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.