The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia

Brett P. Giroir, John H. Johnson, Tracy Brown, Geoffrey L. Allen, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

Abstract

Tumor necrosis factor (TNF) is a protein hormone implicated in the development of septic shock and other pathologic states. However, complexities inherent in detecting TNF synthesis by individual tissues have left the precise origins of this protein undefined. In addition, the possibility that localized TNF production may contribute to the pathogenesis of organ-specific diseases such as type I diabetes has not been explored in vivo. We have developed a transgenic mouse line bearing a reporter gene construct in which the TNF coding sequence and introns are replaced by a chloramphenicol acetyltransferase (CAT) coding sequence. In normal transgenic animals, CAT activity is expressed only in the thymus. When endotoxin is administered to the animals, CAT activity is also evident in kidney, heart, islets of Langerhans, spleen, lung, fallopian tubes, and uterus, but not in other organs. The biosynthesis of CAT in vivo correlated with tissue capacity to secrete TNF in vitro. Thus, TNF was secreted by all the tissues that expressed CAT, including lung, spleen, thymus, uterus/fallopian tubes, pancreatic islets, renal glomeruli, and cultured cardiac cells after exposure to endotoxin.

Original languageEnglish (US)
Pages (from-to)693-698
Number of pages6
JournalJournal of Clinical Investigation
Volume90
Issue number3
DOIs
StatePublished - 1992

Keywords

  • endotoxin
  • septic shock
  • transgenic mice
  • tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)

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