Abstract
16,16-Dimethyl prostaglandin E2 was examined for its ability to inhibit complement-mediatedin vitro hepatocytolysis by an antigen-antibody reaction. In the presence of fresh rat serum as a source of complement, 5-min culture of isolated rat hepatocytes with a monoclonal antibody against a rat liver-specific membranous antigen resulted in a marked, significant elevation in lactate dehydrogenase leakage into the culture medium. However, with heat-inactivated rat serum, such a reaction did not occur, indicating that the hepatocytolysis induced by the antibody was attributable to the membrane damaging action of complement activated by an antigen-antibody reaction. Pretreatment of the hepatocyte with 16,16-dimethyl prostaglandin E2 significantly suppressed the cytolytic reaction induced by the antibody in a concentration-dependent manner. These results show that 16,16-dimethyl prostaglandin E2 is capable of protecting isolated rat hepatocytes against the membrane-damaging insult of activated complement.
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Robert A: Antisecretory, antiulcer, cytoprotective and diarrheogenic properties of prostaglandins. Adv Prostaglandin Thromboxane Res 2:507–520, 1976
Miller TA: Protective effects of prostaglandin against gastric mucosal damage: Current knowledge and proposed mechanism. Am J Physiol 245:G601-G623, 1983
Stachura J, Tarnawski A, Szczudrawa J, Bogdal J, Mach T, Klimczyk B, Kirchmayer S: Cytoprotective effect of 16,16-dimethyl prostaglandin E2 and some drugs on acute galactosamine-induced liver damage in rat. Folia Histochem Cytochem 9:311–318, 1980
Ruwart MJ, Rush BD, Friedle NM, Piper RC, Kolaja GJ: Protective effects of 16,16-dimethyl PGE2 on the liver and kidney. Prostaglandins 21:97–102, 1981
Stachura J, Tarnawski A, Ivey KJ, Mach T, Bogdal J, Szczudrawa J, Klimczyk B: Prostaglandin protection of carbon tetrachloride-induced liver cell necrosis in rats. Gastroenterology 81:211–217, 1981
Rush B, Merritt MV, Kaluzny M, Van Schoick T, Brunden MN, Ruwart M: Studies of the mechanism of the protective action of 16,16-dimethyl PGE2 in carbon tetrachloride induced acute hepatic injury in the rat. Prostaglandins 32:439–455, 1986
Ruwart MJ, Nichols NM, Hedeen K, Rush BD, Stachura J: 16,16-dimethyl PGE2 and fatty acids protect hepatocytes against CCl4-induced damage. In Vitro Cell Dev Biol 8:450–452, 1985
Sato K, Ikeda T, Katami K, Ogawa H: Preparation of monoclonal antibody to hepatocellular membrane and its application to induction of liver cell membrane damage. Acta Pathol Jpn 35:1375–1383, 1985
Sato K, Ikeda T, Kawai F, Osada Y: Isolation and purification of a rat liver-specific antigen from hepatocyte membrane. J Biochem 102:933–938, 1987
Dunnett CW: A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 50:1096–1121, 1955
Raheja KL, Linscheer WG, Cho C: Failure of exogenous prostaglandin to afford complete protection against acetaminophen-induced hepatotoxicity in the rat. J Toxicol Environ Health 15:477–484, 1985
Abecassis M, Falk JA, Makowka L, Dindzans VJ, Falk RE, Levy GA: 16,16-Dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection. J Clin Invest 80:881–889, 1987
Conn HO: Hepatic cytoprotection by prostaglandins: Theories unlimited. Hepatology 8:969–978, 1988
Terano A, Mach T, Stachura J, Tarnawski A, Ivey KJ: Effect of 16,16 dimethyl prostaglandin E2 on aspirin induced damage to rat gastric epithelial cells in tissue culture. Gut 25:19–25, 1984
Ikeda T, Kurebayashi Y: A rat model of acute liver necrosis induced by a monoclonal antibody to liver-specific antigen and complement. Hepatology 13:1152–1157, 1991
Kunkel SL, Thrall RS, Kunkel RG, McCormick JR, Ward PA, Zurier RB: Suppression of immune complex vasculitis in rats by prostaglandin. J Clin Invest 64:1525–1529, 1979
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Kurebayashi, Y., Ikeda, T. & Honda, Y. Protective effect of 16,16-dimethyl prostaglandin E2 on isolated rat hepatocytes against complement-mediated immune attack. Digest Dis Sci 37, 645–649 (1992). https://doi.org/10.1007/BF01296417
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DOI: https://doi.org/10.1007/BF01296417