Signaling mechanisms of altered cellular responses in trauma, burn, and sepsis - Role of Ca2+

Alterations in cellular responses in various organ systems contribute to tr auma-, burn-, and sepsis-related multiple organ dysfunction syndrome. Such alterations in muscle contractile, hepatic metabolic, and neutrophil and T- cell inflammatory-immune responses have been shown to result from cell-sign aling modulations and/or impairments in the respective cell types. Altered Ca2+ signaling would seem to play an important role in the myocardial and v ascular smooth muscle contractile dysfunction in the injury conditions; Ca2 +-linked signaling derangement also plays a crucial role in sepsis-induced altered skeletal muscle protein catabolism and resistance to insulin-mediat ed glucose use. The injury-related increased hepatic gluconeogenesis and ac ute-phase protein response could also be caused by a pathophysiologic up-re gulation of hepatocyte Ca2+-signal generation. The increased oxidant produc tion by neutrophil, a potentially detrimental inflammatory response in earl y stages after burn or septic injuries, seems to result from an up-regulati on of both the Ca2+-dependent as well as Ca2+-independent signaling pathway s. The injury conditions would seem to cause an inappropriate up-regulation of Ca2+-signal generation in the skeletal myocyte, hepatocyte, and neutrop hil, while they lead to a down-regulation of Ca2+ signaling in T cells. The crucial signaling derangement that causes T-cell proliferation suppression seems to be a decrease in the activation of protein tyrosine kinases, whic h subsequently down-regulates Ca2+ signaling. The delineation of cell-signa ling derangements in trauma, burn, or sepsis conditions can lead to develop ment of therapeutic interventions against the disturbed cellular responses in the vital organ systems.