Signaling mechanisms of elevated neutrophil O2/- generation after burn injury

Farideh Sabeh, Philip Hockberger, Mohammed M. Sayeed*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

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 O2/- generation was ascertained by evaluating the effect of treatment of the rats with the Ca2+ entry blocker, diltiazem. There was an overt enhancement of O2/- generation by polymorphonuclear leukocytes from burn rats on days 1, 3, and 7 postburn, with the peak release occurring on day 3 postburn. O2/- generation comparable to the sham was noted on day 10 after the burn. O2/- releases on days 1, 3, and 7 postburn were accompanied by marked elevation of Ca2+ and PKC responses. Like the O2/- 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+](i) and PKC responses as well as O2/- generation in neutrophils in rats on days 1, 3, and 7 after the burn. Because previous studies have shown that increases in [Ca2+](i) precede O2/- generation and degranulation, our results suggest that neutrophil O2/- release enhancement in the early stages after burn injury (e.g., days 1-7 postburn) results from an overactivation of the Ca2+ and PKC signaling pathways. The heightened O2/- generation during the early burn injury phase might play a role in tissue damage in one or more of host organs.

Original languageEnglish (US)
Pages (from-to)R476-R485
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume274
Issue number2 43-2
DOIs
StatePublished - Feb 1998

Keywords

  • Intracellular calcium antagonist
  • Intracellular calcium signaling
  • Protein kinase C activation
  • Rat
  • Reduced nicotinamide adenine dinucleotide phosphate oxidase
  • Thermal injury

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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