The selective engulfment of apoptotic bodies by dendritic cells is mediated by the alpha(v)beta3 integrin and requires intracellular and extracellular calcium.
Dendritic cells derived in vitro from monocytes are known to be poor phagocytes. Here we show that, unlike macrophages, monocyte-derived dendritic cells indeed fail to take up opsonized particles or necrotic cells; however, apoptotic bodies are efficiently engulfed by dendritic cells. The temperature dependence and the sensitivity to cytochalasin D indicate that the apoptotic body engulfment is representative of early stages of phagocytosis. Inhibition studies with ligands for surface molecules involved in recognition of apoptotic bodies, such as vitronectin receptor, CD36 and phosphatidylserine receptor, revealed that apoptotic body engulfment by dendritic cells is mediated preferentially by the vitronectin receptor alpha(v)beta3, while all the receptors, with different efficiency, are engaged in phagocytosis of apoptotic bodies by macrophages. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. Either intra- or extracellular Ca2+ buffering inhibits apoptotic body engulfment by dendritic cells and [Ca2+]i increases, indicating the involvement of both intra- and extracellular Ca2+. In contrast, Ca2+ mobilization is dispensable for macrophage phagocytosis of apoptotic bodies. The different requirements of Ca2+ in macrophages and dendritic cells is possibly due to the differential usage of phagocytic receptors (CD36 vs. alpha(v)beta3) and might reflect different fates of apoptotic bodies in the two cell types.
Rubartelli
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Laboratory of Clinical Pathology, National Institute for Cancer Research, Genova, Italy. annarub@hp380.ist.unige.it
Poggi
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Zocchi
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D017209:Apoptosis / Q000276:immunology*; D018955:CD36 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D019030:Receptors, Vitronectin / Q000378:metabolism*
D018955:CD36 Antigens; D019030:Receptors, Vitronectin; D002118:Calcium