Factors affecting the expression of trifluoroacetylated liver microsomal protein neoantigens in rats treated with halothane.
Previous studies have shown that antibodies in the sera of halothane hepatitis patients recognize trifluoroacetylated liver microsomal proteins (neoantigens) of 100 kDa, 76 kDa, 59 kDa, 57 kDa, and 54 kDa. In the present investigation, factors that might affect the level of expression of the neoantigens were investigated. A study of the time course of neoantigen expression in halothane-treated rats revealed that the 100 kDa, 76 kDa, 59 kDa, and 57 kDa neoantigens were longer-lived than the 54 kDa neoantigen and could be detected in the liver up to a week after the administration of halothane. Pretreatment of rats with isoniazid, which is known to induce cytochrome P-450 IIE1, appeared to increase the expression of each of the neoantigens, whereas inducers of several other forms of cytochrome P-450 had either very little effect or decreased the expression of several of the neoantigens. Female rats appeared to express some of the neoantigens at a higher level than that found in males. Examination of the organ distribution of the trifluoroacetylated neoantigens showed that, of the tissues examined, only the liver contained appreciable levels of the neoantigens. These results indicate that the level of expression and possibly the immunogenicity of the trifluoroacetylated liver neoantigens may be influenced by their half-lives and the repertoire of cytochrome P-450 present in the liver.
Kenna
J G
JG
Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Martin
J L
JL
Satoh
H
H
Pohl
L R
LR
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology; D002642:Chick Embryo; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006221:Halothane / Q000633:toxicity*; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014269:Trifluoroacetic Acid / Q000378:metabolism
D000941:Antigens; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D014269:Trifluoroacetic Acid; D006221:Halothane