Human chemotactic protein

Abstract

A human chemotactic polypeptide, DNA (RNA) encoding it, and a procedure for producing such a polypeptide by recombinant techniques are disclosed. Also disclosed are methods of using the polypeptide for a number of purposes, including: stem cell mobilization, myeloprotection, neuronal protection, treating tumors, wound healing, treating parasitic infection, and regulating hematopoiesis. Also disclosed are polypeptide antagonists and diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention for detecting diseases are also disclosed.

1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide comprising amino acid−26 to amino acid 93 as set forth in SEQ ID NO:2;    (b) a polynucleotide encoding the polypeptide comprising amino acid 1 to amino acid 93 as set forth in SEQ ID NO:2    (c) a polynucleotide which encodes a mature polypeptide having the amino acid sequence expressed by the DNA contained in ATCC™ Deposit No. 75703;    (d) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a), (b) or (c); and    (e) a polynucleotide fragment of the polynucleotide of (a), (b), (c) or (d).    
     
     
         2 . The polynucleotide of  claim 1  wherein the 
 polynucleotide is DNA.    
     
     
         3 . The polynucleotide of  claim 2  which encodes the 
 polypeptide comprising amino acid 1 to 93 of SEQ ID NO:2.    
     
     
         4 . A vector containing the DNA of  claim 2 .  
     
     
         5 . A host cell genetically engineered with the vector of  claim 4 .  
     
     
         6 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 5  the polypeptide encoded by said DNA.  
     
     
         7 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 4 .  
     
     
         8 . A polypeptide comprising a member selected from the group consisting of (i) a polypeptide having the deduced amino acid sequence of SEQ ID NO:2 and fragments, analogs and derivatives thereof; and (ii) a polypeptide encoded by the cDNA of ATCC™ Deposit No. 75703 and fragments, analogs and derivatives of said polypeptide.  
     
     
         9 . The polypeptide of  claim 8  wherein the polypeptide comprises amino acid 1 to amino acid 93 of SEQ ID NO:2.  
     
     
         10 . A compound which inhibits activation of the polypeptide of  claim 8 .  
     
     
         11 . A method for the treatment of a patient having need of MCP-4 comprising: 
 administering to the patient a therapeutically effective amount of the polypeptide of  claim 8 .    
     
     
         12 . The method of  claim 11  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.  
     
     
         13 . A method for the treatment of a patient having need to inhibit an MCP-4 polypeptide comprising: administering to the patient a therapeutically effective amount of the compound of  claim 10 .  
     
     
         14 . A process for diagnosing a disease or a susceptibility to a disease related to an under-expression of MCP-4 comprising: 
 determining a mutation in a nucleic acid sequence encoding MCP-4.    
     
     
         15 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 8  in a sample derived from a host.    
     
     
         16 . A method for identifying compounds which bind to and inhibit activation of the polypeptide of  claim 8  comprising: 
 contacting a cell expressing on the surface thereof a receptor for the polynucleotide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor, with a compound under conditions to permit binding to the receptor; and    detecting the absence of a signal generated from the interaction of the compound with the receptor.    
     
     
         17 . A method for identifying compounds which bind to and activate the polypeptide of  claim 8  comprising: 
 contacting a cell expressing on the surface thereof a receptor for the polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor, with a compound under conditions to permit binding to the receptor; and    detecting the presence of a signal generated from the interaction of the compound with the receptor.    
     
     
         18 . A method for increasing the amount of hematopoietic progenitor cells in the peripheral blood of a host comprising: 
 administering to the host the polypeptide of  claim 8  in an amount effective to increase the amount of hematopoietic progenitor cells in the peripheral blood of the host.    
     
     
         19 . A method for inhibiting destruction of hematopoietic progenitor cells resulting from the treatment of a host with a chemotherapeutic agent, comprising: 
 administering to the host the polypeptide of  claim 8  in an amount effective to inhibit destruction of hematopoietic progenitor cells by a chemotherapeutic agent.    
     
     
         20 . A method for inhibiting degeneration of neuronal cells in a host comprising: 
 administering to a host in need thereof the polypeptide of  claim 8  in an amount effective to inhibit degeneration of the neuronal cells.