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 journalArticle

209 Citations (Scopus)

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, inlets 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
StatePublished - 1992

Fingerprint

Endotoxemia
Tissue Distribution
Chloramphenicol O-Acetyltransferase
Tumor Necrosis Factor-alpha
Fallopian Tubes
Endotoxins
Thymus Gland
Uterus
Spleen
Kidney
Lung
Genetically Modified Animals
Septic Shock
Type 1 Diabetes Mellitus
Islets of Langerhans
Reporter Genes
Introns
Transgenic Mice
Cultured Cells
Proteins

Keywords

  • Endotoxin
  • Septic shock
  • Transgenic mice
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. / Giroir, Brett P.; Johnson, John H.; Brown, Tracy; Allen, Geoffrey L.; Beutler, Bruce.

In: Journal of Clinical Investigation, Vol. 90, No. 3, 1992, p. 693-698.

Research output: Contribution to journalArticle

Giroir, BP, Johnson, JH, Brown, T, Allen, GL & Beutler, B 1992, 'The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia', Journal of Clinical Investigation, vol. 90, no. 3, pp. 693-698.
Giroir, Brett P. ; Johnson, John H. ; Brown, Tracy ; Allen, Geoffrey L. ; Beutler, Bruce. / The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 3. pp. 693-698.
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