Transcriptional regulation of TNF-alpha production in neutropenia.
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.
Daley
Jean M
JM
Department of Surgery, Division of Surgical Research, Rhode Island Hospital and Brown Medical School, Providence, RI 02903, USA. jdaley@lifespan.org
Ivanenko-Johnston
Tetiana
T
Reichner
Jonathan S
JS
Albina
Jorge E
JE
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000502:physiology; D009503:Neutropenia / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018821:CD18 Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase