Effect of ethanol on immune clearance in mice: biphasic alteration of complement-mediated clearance with chronic ethanol ingestion.
Rate constants (k1 through k4) describing complement-mediated and Fc gamma receptor-mediated components of immune clearance were serially determined in BALB/c mice fed ethanol, 10%, in drinking water, for 24 weeks. A branched series, first order reaction sequence model of immune clearance was used to obtain the rate constants from measurements of the clearance of radiolabeled immunoglobulin G-opsonized, murine erythrocytes. A > 50% decrease in complement-mediated clearance occurred, with a nadir of complement-mediated sequestration (k1) and complement-dependent phagocytosis (k4) at 2 weeks (p < 0.003). Mean k1 and k4 rate constant values returned to control levels by week 6, and k1 increased to elevated values in weeks 10 through 20 (p < 0.05). The rate constant governing C3b deactivation and return of deactivated, sensitized cells back to the circulation (k2) was initially normal but decreased in weeks 6 through 24 (p < 0.05). Neither immunoglobulin G Fc gamma receptor-mediated clearance nor the survival of nonsensitized cells were decreased by ethanol. Mice fed ethanol had a mean blood alcohol level of 14.9 +/- 7.2 mmol/L, and their mean weight and serum complement levels did not differ from untreated controls. Complement-dependent sequestration and phagocytosis did not decrease significantly when rechallenged with 10% ethanol, but the decrease in k2 and increase in k1 did occur on rechallenge. Thus, chronic ethanol ingestion in mice is associated with an initial decrease followed by a small rebound increase in complement-mediated clearance of opsonized cells. Fc gamma receptor-mediated clearance is not decreased, and only the rebound increase in complement-mediated clearance is observed on rechallenge. This model provides a unique opportunity to study selective in vivo effects of ethanol on an important function of the immune system as well as to explore the mechanisms of ethanol tolerance in mice.
Messner
R P
RP
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Meryhew
N L
NL
DeMaster
E G
EG
D000284:Administration, Oral; D000818:Animals; D002849:Chromatography, Gas; D003165:Complement System Proteins / Q000032:analysis / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007107:Immune System / Q000502:physiology; D007074:Immunoglobulin G / Q000032:analysis / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D017452:Receptors, IgG / Q000032:analysis / Q000502:physiology; D013997:Time Factors
D007074:Immunoglobulin G; D017452:Receptors, IgG; D000431:Ethanol; D003165:Complement System Proteins