Neutrophil C5a receptor and the outcome in a rat model of sepsis.
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.
Guo
Ren-Feng
RF
Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd., Ann Arbor, Michigan 48109-0602, USA.
Riedemann
Niels C
NC
Bernacki
Kurt D
KD
Sarma
Vidya J
VJ
Laudes
Ines J
IJ
Reuben
Jayne S
JS
Younkin
Ellen M
EM
Neff
Thomas A
TA
Paulauskis
Joseph D
JD
Zetoune
Firas S
FS
Ward
Peter A
PA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015936:Complement C5a / Q000096:biosynthesis; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology*; D011379:Prognosis; D021381:Protein Transport; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000378:metabolism*; D018805:Sepsis / Q000175:diagnosis / Q000276:immunology*; D016019:Survival Analysis
D015703:Antigens, CD; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a