TRAUMA PRIMES CELLS

Abstract

Trauma induces many dramatic and complex changes in host cellular response. This complexity arises from the constellation of signals induced by stress, infection, and injury. Cellular priming, defined as altered response to an agonist induced by an antecedent stimulus, appears to be operative after trauma. If the interaction between two signalling pathways is such that one augments (or depresses) the other, subsequent stimulation of the second "primed" pathway can result in an exaggerated (or attenuated) response. Thus, trauma can prime cells in either a constructive or destructive fashion. Receptor stimulation by priming agents results in the activation of receptor-specific cell signalling pathways. These intracellular signalling pathways can "crosstalk" modifying each other in either a positive of negative fashion. The positive or negative character of interpathway crosstalk eventually manifests itself physiologically as constructive or destructive priming. Could the characteristics of the initial priming predict the sense of the final cellular message? Although the magnitude of both the priming stimulus and subsequent stimuli are important, the temporal relationship between the two stimuli as well as the positive or negative character of their interacting signal pathways need to be considered. It is unclear whether any one characteristic alone determines the sense of the priming effect. In general, it is the interaction of two stimuli with a cell at all three levels (magnitude, character, and temporal relationship) that dictates the final cellular response.