Monocytes arise from stem cells in the bone marrow, enter the circulation and undergo final maturation to macrophages in peripheral tissue. Monocytes/macrophages are essential to wound healing as demonstrated by delayed or incomplete wound healing in animals depleted of monocytes. The inflammatory, proliferative and regenerative phases of wound healing require the participation of monocytes/macrophages either through their phagocytic or secretory function. Particularly important is the secretion of growth promoting factors which are capable of stimulating cellular proliferation and angiogenesis. Monocytes/macrophages may also support the growth of solid tumors through the production of paracrine and angiogenesis factors. Since the majority of monocytes/macrophages which infiltrate a wounded site or a solid tumor are recruited from the peripheral vasculature, factors which regulate monocyte chemotaxis are of considerable importance. The goal of this proposal is to study a monocyte chemoattractant, CF- O, produced by a cell line derived from an osteogenic sarcoma. The proposed studies include deducing the complete amino acid sequence of CF-O through characterization of the CF-O cDNA, studying transcriptional, translational, post-translational and secretory events in the production of CF-O, and describing its binding kinetics and stimulation of monocytes/macrophages. The constitu- tive synthesis of CF-O by a bone-derived cell line provides an opportunity to study a monocyte chemoattractant that may be important in osseous wound healing and in the growth of osseous tumors. This factor may provide insight into the potential control of monocyte chemotaxis by locally produced chemoattractants.
