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PubMed · 15351314

Protective function of complement against alcohol-induced rat liver damage.

Igor L Bykov·Antti Väkevä·Harri A Järveläinen·Seppo Meri·Kai O Lindros
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Abstract

The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

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AlcoholismAnimalsComplement C6Complement System ProteinsCytokinesDisease Models, AnimalLiverLiver Diseases, AlcoholicLiver Function TestsMaleOrgan SizeRNA, MessengerRatsRats, Inbred StrainsReceptors, ProstaglandinReverse Transcriptase Polymerase Chain ReactionJournal ArticleResearch Support, Non-U.S. Gov't

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Igor L Bykov, Antti Väkevä, Harri A Järveläinen, Seppo Meri, Kai O Lindros. 2004. Protective function of complement against alcohol-induced rat liver damage.. https://doi.org/10.1016/j.intimp.2004.06.008

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