Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72

Neil R. Pumford, Brian M. Martin, David Thomassen, Jennifer A. Burris, J. Gerald Kenna, Jackie L. Martin, Lance R. Pohl

Research output: Contribution to journalArticle

Abstract

Immunoblotting studies have previously shown that serum antibodies from halothane hepatitis patients react with several liver microsomal proteins that have been modified by the trifluoroacetyl halide metabolite of halothane. In this study, an 80-kDa protein recognized by the patients' antibodies has been purified from rat liver microsomes and characterized. When the purified trifluoroacetylated 80-kDa and native 80-kDa proteins were employed as test antigens in an enzyme-linked immunosorbent assay, serum antibodies from halothane hepatitis patients reacted with both of these proteins to a significantly greater extent than did serum antibodies from control patients. Amino acid sequence analyses of several hydrolytic peptide fragments of the 80-kDa protein showed that the protein was 99% identical to the deduced amino acid sequence of a murine cDNA of the luminal endoplasmic reticulum protein ERp72. These results indicate that trifluoroacetylated ERp72 in the liver of halothane hepatitis patients may induce immune responses against epitopes present on the covalently altered protein and those present on the native protein and may have a role in halothane hepatitis. In addition, immunoblot and immunohistochemical studies revealed that the 80-kDa protein was present in all tissues studied, but was in highest concentration in liver, adipose tissue, ovaries, and testes and was enriched in specific cells of some organs. In the future, these findings should help define the physiological function of ERp72.

Original languageEnglish (US)
Pages (from-to)609-615
Number of pages7
JournalChemical Research in Toxicology
Volume6
Issue number5
StatePublished - 1993

Fingerprint

Halothane
Endoplasmic Reticulum
Rats
Antibodies
Serum
Proteins
Liver
endoplasmic reticulum glycoprotein p72
Halothane Hepatitis
Tissue
Amino Acids
Immunosorbents
Peptide Fragments
Protein Sequence Analysis
Liver Microsomes
Metabolites
Immunoblotting
Adipose Tissue
Testis
Epitopes

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Pumford, N. R., Martin, B. M., Thomassen, D., Burris, J. A., Gerald Kenna, J., Martin, J. L., & Pohl, L. R. (1993). Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72. Chemical Research in Toxicology, 6(5), 609-615.

Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72. / Pumford, Neil R.; Martin, Brian M.; Thomassen, David; Burris, Jennifer A.; Gerald Kenna, J.; Martin, Jackie L.; Pohl, Lance R.

In: Chemical Research in Toxicology, Vol. 6, No. 5, 1993, p. 609-615.

Research output: Contribution to journalArticle

Pumford, NR, Martin, BM, Thomassen, D, Burris, JA, Gerald Kenna, J, Martin, JL & Pohl, LR 1993, 'Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72', Chemical Research in Toxicology, vol. 6, no. 5, pp. 609-615.
Pumford NR, Martin BM, Thomassen D, Burris JA, Gerald Kenna J, Martin JL et al. Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72. Chemical Research in Toxicology. 1993;6(5):609-615.
Pumford, Neil R. ; Martin, Brian M. ; Thomassen, David ; Burris, Jennifer A. ; Gerald Kenna, J. ; Martin, Jackie L. ; Pohl, Lance R. / Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72. In: Chemical Research in Toxicology. 1993 ; Vol. 6, No. 5. pp. 609-615.
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