INTRODUCTION

One of the regulatory mechanisms controlling the response of excitable cells to stimuli is priming. The term “priming” is used when the prior exposure to a given mediator predisposes a cell to a more effective response to a subsequent stimulus.

Priming has been described for cells as disparate as the neutrophil and myocyte. The initial stimulus (primer) transmits a message to the intracellular signaling machinery that influences the cell's response to a subsequent challenge. This may result, for instance, in an exaggerated inflammatory response in the case of the neutrophil or in an improved tolerance to injury for the myocyte. Neutrophil priming, by agents like tumor necrosis factor alpha (TNF-α), lipopolysac-charide (LPS) and granulocyte/macrophage colony-stimulating factor (GM-CSF), causes a dramatic increase in the capacity to induce tissue injury in response to a subsequent stimulus. This is achieved by the enhancement of superoxide anion generation, degranulation and lipid mediator release. Whereas different cells respond differently to priming stimuli, the intracellular targets appear to be similar; for instance, the priming of both neutrophils and myocytes involves protein kinase C (PKC) activation (although the PKC isoform profile is stimulus-specific and determines the specific functional response of the cell). Recent studies support a key role also for protein tyrosine phosphorylation and enhanced phospholipase D and phosphoinositide 3-kinase-gamma (PI3K-γ) activation in neutrophil priming.