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Neutrophil C5a receptor and the outcome in a rat model of sepsis
Author(s) -
Guo Ren-Feng,
Riedemann Niels C.,
Bernacki Kurt D.,
Sarma Vidya J.,
Laudes Ines J.,
Reuben Jayne S.,
Younkin Ellen M.,
Neff Thomas A.,
Paulauskis Joseph D.,
Zetoune Firas S.,
Ward Peter A.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0009fje
Subject(s) - sepsis , c5a receptor , innate immune system , immunology , receptor , complement system , chemotaxis , western blot , neutrophil extracellular traps , inflammation , biology , internalization , acquired immune system , medicine , immune system , biochemistry , gene
Complement fragment 5a (C5a)–C5a receptor (C5aR) signaling plays an essential role in neutrophil innate immunity. Blockade of either the ligand or the receptor improves survival rates in experimental sepsis. In the current study, sepsis was induced in rats by cecal ligation/puncture. Early in sepsis C5aR content on neutrophils significantly dropped, reached the nadir at 24 h after onset of sepsis, and progressively elevated thereafter. Western‐blot, RT‐PCR, and confocal microscopy analyses revealed that the loss and re‐expression of C5aR during sepsis might be due, at least in part, to the receptor internalization and reconstitution. The reduction and reconstitution of C5aR correlate with the loss and restoration of innate immune functions of blood neutrophils (chemotaxis and reactive oxygen species production), respectively. Quantitative measurements of C5aR on blood neutrophils are highly predictive of survival or death during sepsis. These data suggest that neutrophil C5aR content represents an essential component of an efficient defense system in sepsis and may serve as a prognostic marker for the outcome.