Activation of Complement Components and Reduced Regulator Expression in Alcohol-Induced Liver Injury in the Rat

Differential Contributions of C3, C5, and Decay-Accelerating Factor to Ethanol-Induced Fatty Liver in Mice

“…Making use of monoclonal antibodies developed to neo-epitopes revealed on C3a and C3b/iC3b (31), here we report the presence of C3a in the serum of mice after ethanol exposure (Figure 1). These data are consistent with a previous report using an in vitro complement activation assay demonstrating a deposition of C3 and C8, but not C1, were observed in periportal regions of the liver after ethanol feeding (22). Jarvelainen, et al (22) proposed that this lack of C1 activation suggests that ethanol activates complement via the alternative pathway.…”

“…These data are consistent with a previous report using an in vitro complement activation assay demonstrating a deposition of C3 and C8, but not C1, were observed in periportal regions of the liver after ethanol feeding (22). Jarvelainen, et al (22) proposed that this lack of C1 activation suggests that ethanol activates complement via the alternative pathway. However, the sensitivity and/or the timing of these assays for C1 deposition may have precluded the identification of a role for the classical pathway in mediating the effects of ethanol in liver injury.…”

“…At the time we initiated our experiments, there was a report by Jarvelainen, et al, (22) that ethanol feeding to rats increased deposition of complement proteins C3 and C8, but not C1, in the liver. Lack of C1 deposition suggests that ethanol feeding activates the complement cascade via the lectin and/or alternative pathways (22).…”

“…At the time we initiated our experiments, there was a report by Jarvelainen, et al, (22) that ethanol feeding to rats increased deposition of complement proteins C3 and C8, but not C1, in the liver. Lack of C1 deposition suggests that ethanol feeding activates the complement cascade via the lectin and/or alternative pathways (22). As LPS is a potent activator of the alternative pathway, ethanol-induced activation of the alternative pathway would be consistent with the increased LPS exposure observed in humans after alcohol consumption, as well as in animal models of ethanol exposure (4;14;37).…”

Innate Immunity in Alcohol Liver Disease

“…Chronic alcohol feeding to mice for 4-6 weeks increases activation of C3, as evidenced by increased C3a in the circulation (Pritchard et al, 2007), as well as increased accumulation of C3 or its proteolytic end product C3b/iC3b/C3c in liver (Jarvelainen et al, 2002;Roychowdhury et al, 2009). In rats, chronic alcohol exposure increases C3 activity and decreases expression of Crry, the rat homologue of the complement inhibitory protein CD55/DAF (decayaccelerating factor), and CD59 in the liver (Jarvelainen et al, 2002).…”