Complement-dependent clearance of apoptotic cells by human macrophages.
Apoptotic cells are rapidly engulfed by phagocytes, but the receptors and ligands responsible for this phenomenon are incompletely characterized. Previously described receptors on blood- derived macrophages have been characterized in the absence of serum and show a relatively low uptake of apoptotic cells. Addition of serum to the phagocytosis assays increased the uptake of apoptotic cells by more than threefold. The serum factors responsible for enhanced uptake were identified as complement components that required activation of both the classical pathway and alternative pathway amplification loop. Exposure of phosphatidylserine on the apoptotic cell surface was partially responsible for complement activation and resulted in coating the apoptotic cell surface with C3bi. In the presence of serum, the macrophage receptors for C3bi, CR3 (CD11b/CD18) and CR4 (CD11c/CD18), were significantly more efficient in the uptake of apoptotic cells compared with previously described receptors implicated in clearance. Complement activation is likely to be required for efficient uptake of apoptotic cells within the systemic circulation, and early component deficiencies could predispose to systemic autoimmunity by enhanced exposure to and/or aberrant deposition of apoptotic cells.
Mevorach
D
D
Hospital for Special Surgery, Cornell University Medical College, New York 10021, USA.elkonk@hss.edu
Mascarenhas
J O
JO
Gershov
D
D
Elkon
K B
KB
D017304:Annexin A5 / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology / Q000494:pharmacology; D002460:Cell Line; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D011951:Receptors, Complement / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D009842:Oligopeptides; D010718:Phosphatidylserines; D011951:Receptors, Complement; D003165:Complement System Proteins; C046617:arginyl-glycyl-aspartyl-serine