M-CSF was first characterized as a glycoprotein that induces monocyte and macrophage colony formation from precursors in murine bone marrow cultures. M-CSF is constitutively present at biologically active concentrations in human serum, and binds CD14+ monocytes, and promotes the survival and proliferation of peripheral blood monocytes. In addition, M-CSF enhances monocyte functions such asphagocytic activity, microbial killing, and tumor cell cytotoxicity. It also induces the synthesis of inflammatory cytokines such as IL-1-β, TNF-α, and INF-γ in monocytes. M-CSF induces RANKL in mature osteoclasts, and is consequently a potent stimulator of mature osteoclast resorbing activity. Also, M-CSF induces VEGF in monocytes in human tumors. High levels of M-CSF, mononuclear phagocytes, and VEGF are associated with poor prognosis in patients with cancer. High levels of M-CSF have also been correlated to other pathologies such as pulmonary fibrosis and atherosclerosis. M-CSF binds to its receptor M-CSFR, and this receptor is shared with another ligand, IL-34. Human M-CSF and IL-34 exhibit cross-species specificity by both binding to the human and mouse M-CSF receptors. Respectively, rat M-CSF has 80% and 77% identity with mouse and human M-CSF.