NEUTROPHIL PRIMING - PATHOPHYSIOLOGICAL CONSEQUENCES AND UNDERLYING MECHANISMS

1. Neutrophil priming by agents such as tumour necrosis factor-alpha, granulocyte/macrophage colony-stimulating factor and lipopolysaccharid e causes a dramatic increase in the response of these cells to an acti vating agent; this process has been shown to be critical for neutrophi l-mediated tissue injury both in vitro and in vivo. 2. The principle c onsequence of priming, aside from a direct effect on cell polarization , deformability and integrin/selectin expression, is to permit secreta gogue-induced superoxide anion generation, degranulation and lipid med iator (e.g. leukotriene B-4 and arachidonic acid) release. It is now r ecognized that most priming agents also serve an additional function o f delaying apoptosis and hence increasing the functional longevity of these cells at the inflamed site. 3. The potential mechanisms underlyi ng priming are discussed; current data suggest a dissociation between priming and changes in receptor number and/or affinity, G-protein expr ession, phospholipase C and phospholipase A, activation and changes in intracellular Ca2+ concentration, However, more recent studies suppor t a key role for protein tyrosine phosphorylation and enhanced phospho lipase D and phosphoinositide 3-kinase activity in neutrophil priming. 4. Recent work has also revealed the potential for neutrophils to spo ntaneously and fully 'de-prime' after an initial challenge with platel et-activating factor. This ability of neutrophils to undergo a complet e cycle of priming-de-priming (and re-priming) reveals a previously un recognized flexibility in the control of neutrophil behaviour at an in flamed site.