TY - JOUR
T1 - FcγRIII mediates neutrophil recruitment to immune complexes
T2 - A mechanism for neutrophil accumulation in immune-mediated inflammation
AU - Coxon, Angela
AU - Cullere, Xavier
AU - Knight, Sara
AU - Sethi, Sanjeev
AU - Wakelin, Matthew W.
AU - Stavrakis, George
AU - Luscinskas, Francis W.
AU - Mayadas, Tanya N.
N1 - Funding Information:
This study was supported by National Institutes of Health grants DK51643 and HL65095 (T.N.M.); HL36028, HL53993, HL65090, and HL56985 (F.W.L.); and T32 HL07627 (X.C.). We acknowledge the excellent advice and assistance of Dr. Yaw-Chyn Lim for the flow studies and the helpful suggestions of Dr. William Stegman (Jackson ImmunoResearch Laboratories, Inc.) in preparation of ICs. We thank Drs. Lloyd Klickstein (Brigham and Women's Hospital, Boston, MA) and Timothy Springer (Center for Blood Research, Harvard Medical School, Boston, MA) for K562 cells transfected with Mac-1 and p150,95; Dr. Arthur Beaudet (Baylor College of Medicine, Houston, TX) for CD18 null mice; and Dr. Raymond Camphausen (Genetics Institute, Boston, MA) for recombinant human P-selectin. We gratefully acknowledge Dr. Hans Ochs (University of Washington, School of Medicine, Seattle, WA) for providing blood samples from an LADI patient; and the LADI patient (characterized by Dr. Och) who volunteered to provide blood samples for our study.
PY - 2001
Y1 - 2001
N2 - 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 Fcγ receptor IIIB (FcγRIIIB), and the β2 integrins are additionally required for the subsequent shear-resistant adhesion. The attachment function of FcγRIIIB 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, FcγRIII-deficient mice had a significant reduction in neutrophil recruitment. Thus, the interaction of immune complexes with FcγRIII may mediate early neutrophil recruitment in immune complex-mediated inflammation.
AB - 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 Fcγ receptor IIIB (FcγRIIIB), and the β2 integrins are additionally required for the subsequent shear-resistant adhesion. The attachment function of FcγRIIIB 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, FcγRIII-deficient mice had a significant reduction in neutrophil recruitment. Thus, the interaction of immune complexes with FcγRIII may mediate early neutrophil recruitment in immune complex-mediated inflammation.
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U2 - 10.1016/S1074-7613(01)00150-9
DO - 10.1016/S1074-7613(01)00150-9
M3 - Article
C2 - 11420040
AN - SCOPUS:0034958157
SN - 1074-7613
VL - 14
SP - 693
EP - 704
JO - Immunity
JF - Immunity
IS - 6
ER -