Onset of apoprotein E secretion during differentiation of mouse bone marrow-derived mononuclear phagocytes.

Abstract

A number of macrophage functions were sequentially expressed when the bone marrow precursors of mononuclear phagocytes differentiated in culture in the presence of a specific growth factor, colony-stimulating factor-1. The expression of apoprotein E (ApoE), a major secreted protein of resident peritoneal macrophages, was defined during maturation of adherent bone marrow-derived mononuclear phagocytes into macrophages. By 5 days the bone marrow macrophages were active secretory cells, but few cells contained intracellular immunoreactive ApoE, and little, if any, ApoE was secreted. ApoE secretion was initiated at 9 days and this correlated with an increase in the percentage of macrophages containing intracellular ApoE. The onset of ApoE secertion was selective, and little change occurred in the other major secreted preteins detected by [35S]methionine incorporation. In parallel, the high rate of plasminogen activator secretion, which peaked at 7 days, decreased markedly. ApoE secretion was not associated with altered expression of the macrophage surface antigen, Ia, or with secretion of fibronectin. Virtually all cells in independent colonies of bone marrow-derived macrophages eventually expressed ApoE. The proliferating monocyte/macrophage-like cell lines P388D1, J774.2, WEHI-3, RAW 264.1 and MG1.D+ secreted little or no ApoE. ApoE secretion apparently is developmentally regulated.