C1q governs deposition of circulating immune complexes and leukocyte Fcgamma receptors mediate subsequent neutrophil recruitment.
Inflammation induced by circulating immunoglobulin G-immune complexes (ICs) characterizes many immune-mediated diseases. In this work, the molecular requirements for the deposition of circulating ICs and subsequent acute leukocyte recruitment in mice were elucidated. We show that after intravenous injection, preformed soluble ICs are rapidly deposited in the postcapillary venules of the cremaster microcirculation, secondary to increased vascular permeability. This deposition is dependent on complement C1q. IC deposition is associated with leukocyte recruitment. Leukocyte rolling, which is mediated by P-selectin in the exteriorized cremaster muscle, is not further increased in response to ICs. In contrast, leukocyte rolling velocity is significantly decreased and leukocyte adhesion is significantly increased in the presence of ICs. The IC-mediated slow leukocyte rolling velocity and subsequent adhesion and emigration are dependent on Fcgamma receptors (FcgammaRs), particularly FcgammaRIII, with complement C3 and C5 having no detectable role. These studies suggest a regulatory mechanism of IC deposition and leukocyte trafficking in IC-mediated inflammation requiring C1q and FcgammaRs in sequential, noninteracting roles.
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Tracy
T
Stokol
Peter
P
O'Donnell
Ling
L
Xiao
Sara
S
Knight
George
G
Stavrakis
Marina
M
Botto
Ulrich H
UH
von Andrian
Tanya N
TN
Mayadas
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D001772:Blood Cell Count; D002199:Capillary Permeability / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D015922:Complement C1q / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D018448:Models, Immunological; D018482:Muscle, Skeletal / Q000098:blood supply; D009504:Neutrophils / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D014699:Venules / Q000276:immunology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017452:Receptors, IgG; D015922:Complement C1q