Figure 1.

Schematic representation of surface molecular changes associated with apoptosis. Reduced cell surface molecule expression may occur through metalloprotease-mediated proteolytic shedding. Reduced receptor expression may act to limit apoptotic cell function and generate a distinct cell surface profile from viable cells. For example, reduced expression of CD47 or disabled CD31 may lead to loss of signals preventing phagocytosis. In addition, loss of integrin regulation may result in functional uncoupling in apoptotic cells, leading to cell detachment. Altered association of cell surface molecules with lipid rafts may alter functional activity, including gain-of-function of some receptors, e.g., FcγRIIa on myeloid cells. Altered carbohydrate processing may result in reduced sialic acid exposure and appearance of accessible mannose residues. Downregulation of complement regulatory molecules (e.g., CD55 and CD46) may lead to opsonization with complement components including C3b. Exposure of anionic phospholipids, including phosphatidylserine (PtdSer), allows binding of a broad range of opsonins to apoptotic cells. Protein S and Gas6 bind to PtdSer in a Ca²⁺-dependent manner, whereas milk fat globule EGF-factor 8 (MFG-E8) binds independent of Ca²⁺. Other less well defined apoptotic cell surface changes may allow binding of other opsonins including thrombospondin, C-reactive protein, and surfactant protein A. Finally, proteins with intracellular localizations may appear on the surface of apoptotic cells, including heat-shock proteins and calreticulin. Apoptotic cell surface molecules are shaded blue whereas apoptotic cell opsonins are shaded green.