Trauma-hemorrhage activates signal transduction pathways in mouse splenic T cells.
Severe impairment in the functions of immune-competent cells has been observed following trauma and hemorrhage. Inappropriate release of cytokines during trauma and hemorrhagic shock disrupt T lymphocyte functions and enable cells to activate genes whose products are detrimental for maintaining a much-needed humoral and cell-mediated immunity. The intracellular events for gene activation are mediated by cytoplasmic transcription factors present as nascent (signal transducer and activator of transcription 1 (STAT 1)) or as a complex (nuclear factor kappaB (NF-kappaB)). Receptor-initiated phosphorylation activates these transcription factors prior to their nuclear translocation and binding to cognate DNA sequences. Because T cell functions are critical to efficient functioning of the immune system, we investigated whether expression of transcription factors, STAT1 and NF-kappaB, is perturbed in splenic T cells following trauma and hemorrhage. To study this, enriched T cells harvested from spleens (pooled from three or four mice per group) of sham, trauma (consisting of midline laparotomy), sham+trauma, hemorrhage (blood pressure maintained at approximately 30 mmHg for 90 min followed by adequate fluid resuscitation), and trauma+hemorrhage groups at 16-18 h after surgical procedure were probed for signal expressions in the presence and absence of interferon-gamma using electrophoretic mobility shift and Western immunoblot assay procedures. Hemorrhage with or without trauma induced activation of Janus kinase 1, STAT1, and NF-kappaB in T cells. Stimulation of T cells with interferon-gamma led to activation of all these signals in all groups including experimental controls. STAT1 activation was accompanied by Janus kinase 1 phosphorylation, whereas NF-kappaB activation was mediated by phosphorylation and rapid degradation of IkappaBalpha. These studies demonstrate that hemorrhagic shock, with or without laparotomy, is sufficient to induce activation of transcription factors in splenic T cells. Thus, attempts to prevent the activation of transcription factors following hemorrhage by pharmacologic means might be helpful for maintaining cell-mediated immunity under these conditions.
Samy
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TS
Center for Surgical Research, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Ayala
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A
Catania
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Chaudry
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IH
D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D006470:Hemorrhage / Q000276:immunology* / Q000378:metabolism; D053613:Janus Kinase 1; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011897:Random Allocation; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051841:Transcription Factor RelB; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1