Immune complexes bind preferentially to Fc gamma RIIA (CD32) on apoptotic neutrophils, leading to augmented phagocytosis by macrophages and release of proinflammatory cytokines.
Many human inflammatory diseases are associated with tissue deposition of immune complexes and influx of neutrophils. We show that immune complexes bind preferentially to apoptotic neutrophils via FcgammaRIIA (CD32) and that increased binding is associated with clustering of immune complexes on the plasma membrane of the apoptotic cell. Phagocytosis of immune complex-opsonized apoptotic neutrophils by human macrophages was substantially enhanced (4.4-fold increase compared with control apoptotic neutrophils) and stimulated macrophages to release the proinflammatory cytokines TNF-alpha and IL-6. Immune complexes may perturb the normal pathways for clearance of apoptotic neutrophils by augmenting their clearance at the price of proinflammatory cytokine release. This represents a novel mechanism by which immune complexes may modulate the resolution of inflammation.
Hart
Simon P
SP
Medical Research Council Center for Inflammation Research, University of Edinburgh Medical School, Edinburgh, United Kingdom. s.hart@ed.ac.uk
Alexander
Karen M
KM
Dransfield
Ian
I
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D001666:Binding Sites, Antibody; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D016207:Cytokines; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D015850:Interleukin-6; D009895:Opsonin Proteins; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine