Selective, prolonged alteration of complement-mediated immune clearance after acute exposure of mice to ethanol.
A selective and prolonged alteration in complement-mediated immune clearance was found in mice given a single intraperitoneal injection of ethanol. Rate constants for the separate components of complement- and IgG Fc gamma-mediated clearance were determined using a branched series, first-order reaction sequence model and measurements of the disappearance of radiolabeled IgG-opsonized murine erythrocytes from the circulation of BALB/c mice. The rate constant governing immune clearance mediated by IgG Fc gamma receptors (k3) decreased to 16% of control at 1 hr after ethanol injection but returned to normal in 72 hr. A > 50% decrease in complement-mediated clearance occurred, with a nadir of complement-mediated sequestration (k1) and complement-dependent phagocytosis (k4) at 1 hr (P < 0.001). In this case, however, k1 and k4 rate constant values did not return to control levels until 6 weeks after the injection of ethanol. The rate constant governing C3b deactivation and release of deactivated, sensitized cells back to the circulation before they undergo phagocytosis (k2) was initially normal, but decreased in Week 6 and remained low to the end of the observation period at 22 weeks (P < 0.0001). These changes resulted in a major reduction in overall complement-mediated immune clearance up to 4 weeks after the ethanol injection. The change to normal rates for sequestration and phagocytosis coupled with decreased deactivation and release at 6 weeks postinjection resulted in a small increase in overall complement-mediated clearance that persisted through Week 22.
Messner
R P
RP
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Meryhew
N L
NL
DeMaster
E G
EG
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D003165:Complement System Proteins / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007728:Kupffer Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects*; D017463:Receptors, Complement 3b / Q000502:physiology
D017463:Receptors, Complement 3b; D000431:Ethanol; D003165:Complement System Proteins; D000426:Alcohol Dehydrogenase