Transcriptional regulation of TNF-alpha production in neutropenia

Am J Physiol Regul Integr Comp Physiol. 2005 Feb;288(2):R409-12. doi: 10.1152/ajpregu.00322.2004. Epub 2004 Sep 30.


Neutropenia has been shown to markedly increase plasma TNF-alpha concentration after LPS injection and to enhance LPS-induced mortality. Experiments reported here demonstrate that the 15-fold higher plasma TNF-alpha concentration elicited by LPS in neutropenic vs. nonneutropenic unanesthetized mice correlated with increased hepatic and splenic, but not pulmonary, TNF-alpha mRNA. Core 2 beta-1,6-N-acetylglucosaminyltransferase-null and CD18-deficient mice also exhibited exaggerated plasma TNF-alpha responses to LPS injection. Findings suggest that extravasated neutrophils inhibit systemic TNF-alpha production and that they do so through organ-selective mechanisms involving CD18 integrin and selectin binding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD18 Antigens / physiology
  • Gene Expression Regulation
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • N-Acetylglucosaminyltransferases / physiology
  • Neutropenia / metabolism*
  • RNA, Messenger / metabolism
  • Spleen / metabolism
  • Transcription, Genetic / physiology*
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • CD18 Antigens
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • N-Acetylglucosaminyltransferases
  • beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase