H Liang1, Z Wang, P Zhu. 1. Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongquing 400042.
Abstract
OBJECTIVE: To study the relationship between the suppression of T cell functions and the change of signal transduction in traumatized mice. METHODS: 60 Balb/c mice were randomized into six groups: normal control, 1st, 2nd, 4th, 7th, 10th day posttrauma (n = 10). A murine closed trauma model was used, T cells were separated from splenocytes using nylon column. T cell functions were determined and their relationship with intracellular signal transduction was investigated. RESULTS: Interleukin 2 (IL-2) mRNA and IL-2 receptor alpha (IL-2R alpha) mRNA levels were decreased in activated T cells from traumatized mice, IL-2 production, IL-2R alpha expression and T lymphocytes transformation were suppressed. cAMP contents in activated T cells were increased after trauma while cGMP contents, free calcium (Ca2+) concentration and protein kinase C (PKC) activities were decreased. These changes were closely related to the suppression of T cell functions. In addition, adenylate cyclase (AC) and protein kinase A (PKA) activities were increased while cAMP-dependent phosphodiesterase (cAMP-PDE), calmodulin (CaM), CaM-dependent protein kinase (CaM-PK) activities were decreased. Levamisole (a stimulator of cGMP), H-8 (an inhibitor of PKA), A23187 (an ionophore of Ca2+) and TPA (an activator of PKC) could in vitro elevate activated T cell functions after trauma in various degrees. CONCLUSIONS: Alteration in the pathway of signal transduction following trauma related to cyclic nucleotide and phosphatidylinositol metabolism in activated T cells participate in mediating the suppressive progress of T cell functions.
OBJECTIVE: To study the relationship between the suppression of T cell functions and the change of signal transduction in traumatized mice. METHODS: 60 Balb/c mice were randomized into six groups: normal control, 1st, 2nd, 4th, 7th, 10th day posttrauma (n = 10). A murine closed trauma model was used, T cells were separated from splenocytes using nylon column. T cell functions were determined and their relationship with intracellular signal transduction was investigated. RESULTS:Interleukin 2 (IL-2) mRNA and IL-2 receptor alpha (IL-2R alpha) mRNA levels were decreased in activated T cells from traumatized mice, IL-2 production, IL-2R alpha expression and T lymphocytes transformation were suppressed. cAMP contents in activated T cells were increased after trauma while cGMP contents, free calcium (Ca2+) concentration and protein kinase C (PKC) activities were decreased. These changes were closely related to the suppression of T cell functions. In addition, adenylate cyclase (AC) and protein kinase A (PKA) activities were increased while cAMP-dependent phosphodiesterase (cAMP-PDE), calmodulin (CaM), CaM-dependent protein kinase (CaM-PK) activities were decreased. Levamisole (a stimulator of cGMP), H-8 (an inhibitor of PKA), A23187 (an ionophore of Ca2+) and TPA (an activator of PKC) could in vitro elevate activated T cell functions after trauma in various degrees. CONCLUSIONS: Alteration in the pathway of signal transduction following trauma related to cyclic nucleotide and phosphatidylinositol metabolism in activated T cells participate in mediating the suppressive progress of T cell functions.