TY - JOUR
T1 - C5a initiates the inflammatory cascade in immune complex peritonitis
AU - Godau, Jeanne
AU - Heller, Tanja
AU - Hawlisch, Heiko
AU - Trappe, Matthew
AU - Howells, Elaine
AU - Best, Jennifer
AU - Zwirner, Jörg
AU - Verbeek, J. Sjef
AU - Hogarth, P. Mark
AU - Gerard, Craig
AU - Van Rooijen, Nico
AU - Klos, Andreas
AU - Gessner, J. Engelbert
AU - Köhl, Jörg
PY - 2004/9/1
Y1 - 2004/9/1
N2 - Immune complex (IC)-induced inflammation is integral to the pathogenesis of several autoimmune diseases. ICs activate the complement system and interact with IgG FcγR. In this study, we demonstrate that activation of the complement system, specifically generation of C5a, initiates the neutrophilic inflammation in IC peritonitis. We show that ablation of C5a receptor signaling abrogates neutrophil recruitment in wild-type mice and prevents the enhancement of neutrophil migration seen in FcγRIIB-/- mice, suggesting that C5aR signaling is the crucial initial event upstream of FcγR signaling. We also provide evidence that C5a initiates the inflammatory cascade both directly, through C5aR-mediated effector functions on infiltrating and resident peritoneal cells, and indirectly, through shifting the balance between activating and inhibitory FcγRs on resident cells toward an inflammatory phenotype. We conclude that complement activation and C5a generation are prerequisites for IC-induced inflammation through activating FcγR, which amplifies complement-induced inflammation in autoimmunity.
AB - Immune complex (IC)-induced inflammation is integral to the pathogenesis of several autoimmune diseases. ICs activate the complement system and interact with IgG FcγR. In this study, we demonstrate that activation of the complement system, specifically generation of C5a, initiates the neutrophilic inflammation in IC peritonitis. We show that ablation of C5a receptor signaling abrogates neutrophil recruitment in wild-type mice and prevents the enhancement of neutrophil migration seen in FcγRIIB-/- mice, suggesting that C5aR signaling is the crucial initial event upstream of FcγR signaling. We also provide evidence that C5a initiates the inflammatory cascade both directly, through C5aR-mediated effector functions on infiltrating and resident peritoneal cells, and indirectly, through shifting the balance between activating and inhibitory FcγRs on resident cells toward an inflammatory phenotype. We conclude that complement activation and C5a generation are prerequisites for IC-induced inflammation through activating FcγR, which amplifies complement-induced inflammation in autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=4344600286&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.173.5.3437
DO - 10.4049/jimmunol.173.5.3437
M3 - Journal articles
C2 - 15322209
AN - SCOPUS:4344600286
SN - 0022-1767
VL - 173
SP - 3437
EP - 3445
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -