MACROPHAGE COLONYSTIMULATING FACTOR (rM-CSF) STIMULATES PINOCYTOSIS IN BONE MARROW-DERIVED MACROPHAGES

Polypeptide growth factors are involved in the regulation ofcell proliferation (1). These factors bind to specific receptors on the cell surface, stimulating the formation of intracellular second messengers that elicit a variety of responses . Transient increases in intracellular pH (2) and calcium concentration (3) can occur soon after growth factor addition . Other early responses induced by epidermal growth factor (EGF)' (4-9), platelet-derived growth factor (5, 1Q), insulin (7, 11, 12), and insulinlike growth factor-1 (4, 5, 7), include cell ruffling, stimulation of pinocytosis, and redistribution ofcell surface receptors . Ultimately, binding ofgrowth factors to responsive cells leads to later activities such as initiation of DNA synthesis and mitosis. A correlation between growth factor-stimulated pinocytosis and proliferation was seen in studies of EGF treatment of normal human fibroblasts (8, 13). However, it is not known how the initial signal elicited by mitogen binding leads to such distinct activities as pinocytosis and mitosis, or whether the coincidence of the two responses is significant. We chose to study the regulation of growth factor-stimulated pinocytosis in macrophages because their growth factor, CSF1, and its receptor have been characterized, and because solute and membrane movement within these cells are active and well-documented processes (reviewed in references 14, 15). Moreover, PMA treatment ofresident, proteose peptone-elicited, and thioglycollate-elicited macrophages stimulates cell spreading and pinocytosis (16) . Addition ofPMAto bone marrow-derived macrophages (BMM) stimulates cell ruling and the formation oflarge, phasebright cytoplasmic vesicles, termed macropinosomes (17) . These organelles had been observed in previous investigations ofgrowth factor-stimulated pinocytosis (18) . The morphological changes in BMM correlated with increased flow of Lucifer YellowCH (LY) through the endocytic compartment, and added pinocytosis to the list of PMAstimulated responses that mimicknown mitogen-elicited responses. We therefore asked if the macrophage-specific growth factor, CSF1, stimulated pinocytosis in a