Transcriptional regulation of TNF-α production in neutropenia

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