Fc gamma RIII mediates neutrophil recruitment to immune complexes. a mechanism for neutrophil accumulation in immune-mediated inflammation.
Neutrophil accumulation is a hallmark of immune complex-mediated inflammatory disorders. Current models of neutrophil recruitment envision the capture of circulating neutrophils by activated endothelial cells. We now demonstrate that immobilized immune complexes alone support the rapid attachment of neutrophils, under physiologic flow conditions. Initial cell tethering requires the low-affinity Fc gamma receptor IIIB (Fc gamma RIIIB), and the beta(2) integrins are additionally required for the subsequent shear-resistant adhesion. The attachment function of Fc gamma RIIIB may be facilitated by its observed presentation on neutrophil microvilli. In vivo, in a model of acute antiglomerular basement membrane nephritis in which immune complexes are accessible to circulating neutrophils, Fc gamma RIII-deficient mice had a significant reduction in neutrophil recruitment. Thus, the interaction of immune complexes with Fc gamma RIII may mediate early neutrophil recruitment in immune complex-mediated inflammation.
Coxon
A
A
Department of Pathology, Brigham and Women's Hospital and, Harvard Medical School, 221 Longwood Avenue, 02115, Boston, MA, USA
Cullere
X
X
Knight
S
S
Sethi
S
S
Wakelin
M W
MW
Stavrakis
G
G
Luscinskas
F W
FW
Mayadas
T N
TN
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies; D001485:Basement Membrane / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion; D058851:GPI-Linked Proteins; D006801:Humans; D020014:K562 Cells; D007678:Kidney Glomerulus / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D001323:Autoantibodies; D018821:CD18 Antigens; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; C051951:antiglomerular basement membrane antibody