DIFFERENTIAL EXPRESSION OF CD14, CD36 AND THE LDL RECEPTOR ON HUMAN MONOCYTE-DERIVED MACROPHAGES - A NOVEL CELL-CULTURE SYSTEM TO STUDY MACROPHAGE DIFFERENTIATION AND HETEROGENEITY

Macrophages are key players in many aspects of human physiology and di sease. It has been hypothesized that in a given microenvironment monoc ytes differentiate into specific subpopulations with distinct function s. In order to study the role of macrophage heterogeneity in atherogen esis, we established a novel isolation and culture technique for human monocyte-derived macrophages. The present technique does not select f or monocyte subpopulations prior to the onset of differentiation. Mono cytes were cultured for 2 weeks in the presence of autologous lymphocy tes before being plated quantitatively. They differentiated into matur e macrophages in terms of morphology, lipid composition, and biologica l activity. Based on phagocytic activity as well as on the expression of CD14, CD36, and the low-density lipoprotein (LDL) receptor, we have identified macrophage subpopulations that may play distinct roles in atherogenesis. While virtually all adherence-purified monocytes expres sed CD14, CD36, and the LDL-R, we characterized three subpopulations o f macrophages based on the expression of these antigens: CD36(+)CD14(- )LDL-R- (58+/-12%), CD36(+)CD14(+)LDL-R+(18+/-5%), the remaining cells being CD36(-)CD14(-) LDL-R-. The first two subsets decreased in size during further differentiation (51+/-12% and 8+/-3%, respectively). Ou r culture technique may also serve as a good model for studying the im plications of macrophage heterogeneity in diseases other than atherosc lerosis.