Neutrophil migration during endotoxemia

Endotoxemia is marked by a global activation of inflammatory responses, whi ch can lead to shock, multiple organ failure, and the suppression of immune and wound healing processes. Neutrophils (PMNs) play a central role in som e of these responses by accumulating in tissues and releasing reactive oxyg en species and proteases that injure host structures. This review focuses o n altered PMN migratory responses that occur during endotoxemia and their c onsequences in the development of pulmonary infection. The inflammatory med iators that might be responsible for these altered responses are discussed. Time oxidant potential of PMNs is increased after exposure to endotoxin bo th in vitro and during clinical and experimental endotoxemia. However, othe r functions such as chemotaxis and phagocytosis are often depressed in thes e same cells, Endotoxin exposure renders PMNs hyperadhesive to endothelium. The sum of these effects produces activated inflammatory cells that are in capable of leaving the vasculature, As such, the endotoxic PMN is more like ly to promote tissue injury from within microvascular beds than to clear pa thogens front extravascular sites. Moreover, the functional characteristics of endotoxic PMNs are similar to those observed during trauma, burn injury , sepsis, surgery, and other inflammatory conditions, Accordingly, several clinical conditions might have a common effector in the activated, yet migr atorially dysfunctional, PMN. Direct effects of endotoxin on PMNs as well a s effects of endogenous mediators released during endotoxemia are discussed . Understanding PMN behavior during endotoxemia may provide basic and criti cal insights that can be applied to a number of inflammatory scenarios.