CD36 IS REQUIRED FOR PHAGOCYTOSIS OF APOPTOTIC CELLS BY HUMAN MACROPHAGES THAT USE EITHER A PHOSPHATIDYLSERINE RECEPTOR OR THE VITRONECTIN RECEPTOR (ALPHA(V)BETA(3))

In vivo, apoptotic cells are efficiently removed by professional or no nprofessional phagocytes, a process thought to be essential for tissue remodeling and resolution of inflammation. Macrophages recognize apop totic cells by several mechanisms, including recognition of exposed ph osphatidylserine (PS); however, PS recognition on apoptotic cells has not been identified as a feature of human macrophages, The purpose of this study was to determine whether human monocyte-derived macrophages could be stimulated to recognize PS, defined as inhibition of phagocy tosis by PS-containing liposomes. We also assessed the potential roles for scavenger receptors, CD14, and lectins. Uptake of apoptotic neutr ophils into unstimulated macrophages was blocked about 50% by Arg-Gly- Asp-Ser and anti-alpha(v), and up to 20% by oxidized low density lipop rotein and N-acetylglucosamine, implying a major role for integrin and minor roles for scavenger and lectin receptors, Uptake into macrophag es stimulated with beta-1,3-glucan was blocked 50% by PS liposomes and 40% by oxidized low density lipoprotein, suggesting that the macropha ges had switched from using integrin to recognition of PS, MEM-18 and 61D3 (anti-CD14 mAbs) were poor inhibitors of apoptotic neutrophil upt ake, but good inhibitors of apoptotic lymphocyte uptake. The switch to PS recognition was accompanied by down-regulation of alpha(v)beta(3) expression and function. Anti-CD36 blocked uptake into unstimulated or stimulated macrophages,suggesting CD36 involvement not only with the alpha(v)beta(3) integrin mechanism (as previously reported) but also w ith PS recognition. A maximum of 70% inhibition was achieved by combin ing anti-CD36 with either anti-a(v) or PS liposomes.