REGULATED EXPRESSION OF CD36 DURING MONOCYTE-TO-MACROPHAGE DIFFERENTIATION - POTENTIAL ROLE OF CD36 IN FOAM CELL-FORMATION

CD36 is an 88-kD integral membrane glycoprotein expressed on monocytes , platelets, and certain microvascular endothelium serving distinct ce llular functions both as an adhesive receptor for thrombospondin, coll agen, and Plasmodium falciparom-infected erythrocytes, and as a scaven ger receptor for oxidized low-density lipoprotein and apoptotic neutro phils. In this study, we examined the expression of CD36 during in vit ro differentiation of peripheral blood monocytes into culture-derived macrophages. Steady-state mRNA levels of CD36 showed a transient eight fold increase during monocyte-to-macrophage differentiation, peaking a t the early macrophage stage (days 3 or 4 in culture), following a gra dual decrease back to baseline levels by the mature macrophage stage ( days 7 or 8 in culture). Immunoblotting with monoclonal antibodies to CD36 supported this transient, yet significant (8- to 10-fold) increas e in total protein levels of CD36. The increased CD36 protein was obse rved at the plasma membrane, whereas an intracellular pool of CD36 was also detected from day 2 to day 6 in culture through indirect immunof luorescence. A concomitant twofold increase in the cells' ability to b ind I-125-thrombospondin at the early macrophage stage (day 4) verifie d the functional competency of the plasma membrane localized CD36, and supported the presence of an intracellular pool of CD36. The in vitro differentiated macrophages as well as alveolar macrophages remained r esponsive to macrophage colony-stimulating factor (M-CSF), a known tra nscriptional regulator of monocyte CD36. The M-CSF-induced macrophages resulted in enhanced foam cell formation, which was inhibitable with monoclonal antibodies to CD36, Thus, the transient expression of CD36 during monocyte-to-macrophage differentiation, and the ability of M-CS F to maintain macrophage CD36 at elevated levels, may serve as a criti cal process in dictating the functional activity of CD36 during inflam matory responses and atherogenesis. (C) 1996 by The American Society o f Hematology.