Activation of complement components and reduced regulator expression in alcohol-induced liver injury in the rat.
The purpose of this study was to evaluate the possible contribution of complement-mediated inflammation to the development of alcoholic liver disease. Male Wistar rats were fed ethanol by liquid diet in a model that results in continuous ethanol intoxication and induces early signs of alcoholic liver injury. After a six-week study period liver samples were analyzed for the deposition of complement components (C1, C3, and C8) and expression of cell membrane-bound regulators (Crry and CD59). Activation of the homologous complement system in vitro was tested by treating frozen liver sections with normal rat serum (NRS). Immunohistochemical analysis showed deposits of C8 in the liver sections of ethanol-treated rats. When frozen liver sections from these rats were treated with NRS, periportal deposition of both C3 and C8, but only slight C1 deposition, was observed. Immunohistochemical and Western blot analysis both revealed a reduced expression of the complement regulators Crry and CD59. These results suggest an induction of complement-activating capacity in the liver after chronic ethanol treatment. Lack of C1 deposition in the lesions suggests that complement activation occurs primarily via the alternative pathway. The reduced expression of the critical complement regulatory proteins Crry and CD59 may sensitize the liver to complement-mediated damage.
Järveläinen
Harri A
HA
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki University Central Hospital, Alcohol Research Center, National Public Health Institute, Helsinki, Finland.
Väkevä
Antti
A
Lindros
Kai O
KO
Meri
Seppo
S
D000818:Animals; D000954:Antigens, Surface; D015153:Blotting, Western; D018957:CD59 Antigens / Q000096:biosynthesis* / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D007150:Immunohistochemistry; D008108:Liver Diseases, Alcoholic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000276:immunology
D000954:Antigens, Surface; D018957:CD59 Antigens; C513105:Cr1l protein, rat; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D000431:Ethanol; D003165:Complement System Proteins