LEPTIN CAN INDUCE PROLIFERATION, DIFFERENTIATION, AND FUNCTIONAL ACTIVATION OF HEMATOPOIETIC-CELLS

Many cytokines exert their biological effect through members of the he mopoietin receptor family, Using degenerate oligonucleotides to the co mmon WSXWS motif, we have cloned from human hemopoietic cell cDNA libr aries various forms of the receptor that was recently shown to bind th e obesity hormone, leptin, mRNAs encoding long and short forms of the human leptin receptor were found to be coexpressed in a range of human and marine hemopoietic organs, and a subset of cells from these tissu es bound leptin at the cell surface, Ectopic expression in murine Ba/F 3 and M1 cell lines revealed that the long, but not the short, form of the leptin receptor can signal proliferation and differentiation, res pectively. In cultures of murine or human marrow cells, human leptin e xhibited no capacity to stimulate cell survival or proliferation, but it enhanced cytokine production and phagocytosis of Leishmania parasit es by murine peritoneal macrophages. Our data provide evidence that, i n addition to its role in fat regulation, leptin may also be able to r egulate aspects of hemopoiesis and macrophage function.