Trauma-hemorrhage activates signal transduction pathways in mouse splenic T cells

Academic Article


  • 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 κB (NF-κB)). 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-κB, 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 ∼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-γ using electrophoretic mobility shift and Western immunoblot assay procedures. Hemorrhage with or without trauma induced activation of Janus kinase 1, STAT1, and NF-κB in T cells. Stimulation of T cells with interferon-γ led to activation of all these signals in all groups including experimental controls. STAT1 activation was accompanied by Janus kinase 1 phosphorylation, whereas NF-κB activation was mediated by phosphorylation and rapid degradation of IκBα. These studies demonstrate that hernorrhagic 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.
  • Authors

    Published In

  • Shock  Journal
  • Author List

  • Samy TSA; Ayala A; Catania RA; Chaudry IH
  • Start Page

  • 443
  • End Page

  • 450
  • Volume

  • 9
  • Issue

  • 6