Anti-himf antibodies to treat lung diseases

Abstract

Hypoxia induced mitogenic factor (HIMF) is a member of the “found in inflammatory zone” (FIZZ)/resistin family of proteins and has potent mitogenic, angiogenic, and vasoconstrictive effects in the lung vasculature. The receptor/binding partners for this family of proteins have been largely unknown. We identified Bruton's tyrosine kinase (BTK) as a functional HIMF binding partner through GST-HIMF pull-downs and mass spectrometry. Using primary cultured HIMF-stimulated murine bone marrow cells, we demonstrated that BTK was recruited to the leading edge of the cells. A transwell migration assay showed that treatment with recombinant murine HIMF induced migration of primary cultured bone marrow cells, which was completely blocked by a BTK inhibitor. In vivo studies revealed that HIMF can stimulate angiogenesis in the hypoxic tissue. Our results indicate that HIMF may act as a chemotactic molecule in stimulating the migration of leukocytes/EPCs from bone marrow to targeted tissues through activation of the BTK pathway.

1 - 19 . (canceled) 
     
     
         20 . A method to diagnose pulmonary hypertension, comprising:
 determining amount of HIMF (SEQ ID NO: 1 or 2) in a serum sample of a subject;   identifying a serum sample that has an amount of HIMF greater than an amount of HIMF in normal, non-pulmonary hypertensive controls as belonging to a subject with pulmonary hypertension.   
     
     
         21 . The method of  claim 20  wherein the amount of HIMF is determined using an antibody which specifically binds to resistin. 
     
     
         22 . The method of  claim 20  wherein the amount of HIMF is determined using an antibody which specifically binds to RELMbeta. 
     
     
         23 . The method of  claim 20  wherein the amount is determined using an enzyme-linked immunosorbent assay.