Expression of xenobiotic-metabolizing cytochrome P450s in human pulmonary tissues

Arch Toxicol Suppl. 1998;20:465-9. doi: 10.1007/978-3-642-46856-8_41.

Abstract

The purpose of the study was to obtain a comprehensive picture of the expression of cytochrome P450s (CYP) in the human lung, broncho-alveolar macrophages (BAM), and peripheral blood lymphocytes. The methods used were reverse transcriptase-polymerase chain reaction (RT-PCR) with gene-specific primers and immunohistochemistry with specific anti-peptide antibodies. In RT-PCR, CYPs 1A1, 2B6/7, 2E1, 2F1, 3A5 and 4B1 were detected in cDNA prepared from whole lung tissue. BAMs expressed CYPs 1B1, 2B6/7, 2C, 2E1, 2F1, 3A5 and 4B1. These tissues lacked CYPs 1A2, 2A6, 2D6, and 3A7. In peripheral blood lymphocytes, only CYP1B1 and CYP2E1 mRNAs were consistently detected. In immunohistochemistry with anti-CYP3A antibodies, epithelial staining of CYP3A5 was observed in 100% of individuals, while only about 20% exhibited CYP3A4 staining. CYP3A5 protein was localized in the bronchial wall, bronchial glands, bronchiolar epithelium, alveolar epithelium, vascular endothelium and alveolar macrophages. The results indicate that several different xenobiotic-metabolizing CYPs are present in the human lung, possibly contributing to in situ activation of pulmonary procarcinogens.

Publication types

  • Comparative Study

MeSH terms

  • Cytochrome P-450 Enzyme System / analysis*
  • Humans
  • Isoenzymes / analysis*
  • Lung / enzymology*
  • Lymphocytes / enzymology
  • Macrophages, Alveolar / enzymology*
  • RNA, Messenger

Substances

  • Isoenzymes
  • RNA, Messenger
  • Cytochrome P-450 Enzyme System