Neutrophil degranulation and abnormal chemotaxis after thermal injury.

Abstract

Abstract The burn patient develops a leukocyte chemotactic defect that is thought to predispose to infection. In an attempt to better understand the mechanism of abnormal polymorphonuclear leukocyte (PMN) chemotaxis after thermal injury, peripheral blood PMN from 15 burn patients were studied 21 times for chemotaxis to Escherichia endotoxin-activated serum and random migration to buffer (51Cr radioassay) as well as total cellular lysozyme and β-glucuronidase. Chemotactic activity and random migration were depressed significantly during days 5 to 15 post-injury (p<0.01 and p<0.02, respectively); the severity of the defect was a function of burn-wound area (p<0.05). The migration response on other days was normal. Sepsis and mortality were more frequent in those patients in whom chemotaxis was less than 65% normal. The PMN-specific granule enzyme lysozyme, but not the azurophil granule enzyme β-glucuronidase, was reduced significantly in patients with chemotactically less responsive PMN (p<0.05), and the degree of lysozyme reduction was related to the extent of thermal injury (p<0.02). In addition, the severity of the defect in chemotactic responsiveness was a function of the decrease in intracellular lysozyme (p<0.001). In vitro studies we published previously, assessing the effect of secretagogues on normal PMN chemotaxis, showed that degranulation of greater than 30% PMN-specific granule contents inhibited chemotactic responsiveness. The data in the current paper indicate that peripheral blood neutrophils from burn patients have diminished their specific granule contents and support the concept that secretion of specific granules in vivo may result in defective PMN chemotaxis by mechanisms similar to that noted by degranulation in vitro.