Signaling mechanisms of elevated neutrophil O 2 − generation after burn injury

Abstract

A full skin thickness burn injury was produced in anesthetized rats by exposing 25% of total body surface area to 98°C water for 10 s. Sham (exposed to 37°C water) and burn rats were killed 1, 3, 7, or 10 days later. The role of Ca2+signaling and Ca2+-related protein kinase C (PKC) activation in neutrophil[Formula: see text] generation was ascertained by evaluating the effect of treatment of the rats with the Ca2+entry blocker, diltiazem. There was an overt enhancement of[Formula: see text] generation by polymorphonuclear leukocytes from burn rats on days 1, 3, and 7 postburn, with the peak release occurring on day 3 postburn.[Formula: see text] generation comparable to the sham was noted on day 10 after the burn.[Formula: see text] releases on days 1, 3, and 7 postburn were accompanied by marked elevation of [Formula: see text] and PKC responses. Like the [Formula: see text] release, intracellular Ca2+concentration ([Ca2+]i) response on day 10 after burn was suppressed to levels found in the sham group. The treatment of burn rats with diltiazem prevented the upregulation of both [Ca2+]iand PKC responses as well as [Formula: see text]generation in neutrophils in rats on days 1, 3, and 7 after the burn. Because previous studies have shown that increases in [Ca2+]iprecede [Formula: see text] generation and degranulation, our results suggest that neutrophil[Formula: see text] release enhancement in the early stages after burn injury (e.g., days 1- 7postburn) results from an overactivation of the[Formula: see text] and PKC signaling pathways. The heightened [Formula: see text] generation during the early burn injury phase might play a role in tissue damage in one or more of host organs.