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Am J Physiol Regul Integr Comp Physiol (September 30, 2004). doi:10.1152/ajpregu.00322.2004
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Submitted on May 14, 2004
Accepted on September 23, 2004

Transcriptional regulation of TNF-{alpha} production in neutropenia

Jean M Daley1*, Tetiana Ivanenko-Johnston1, Jonathan S Reichner1, and Jorge E Albina1

1 Department of Surgery, Division of Surgical Research, Rhode Island Hospital and Brown Medical School, Providence, RI, USA

* To whom correspondence should be addressed. E-mail: jdaley{at}lifespan.org.

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 fifteen-fold higher plasma TNF-{alpha} concentration elicited by LPS in neutropenic vs. non-neutropenic unanesthetized mice correlated with increased hepatic and splenic, but not pulmonary, TNF-{alpha} mRNA. Core 2 {beta}-1,6N-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.




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