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INFLAMMATION AND CYTOKINES

Transcriptional regulation of TNF- production in neutropenia

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

Submitted 14 May 2004 ; accepted in final form 23 September 2004

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

inflammation; neutrophil; lipopolysaccharide; CD18; Core 2 oligosaccharide

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