Lyn- and ERK-mediated vs. Ca2+-mediated neutrophil O Formula responses with thermal injury

Nadeem Fazal, Walid M. Al-Ghoul, Megan J. Schmidt, Mashkoor A. Choudhry, Mohammed M. Sayeed


We evaluated the dependency of neutrophil O 2 production on PTK-Lyn and MAPK-ERK1/2 in rats after thermal injury. Activation of PTK-Lyn was assessed by immunoprecipitation. Phosphorylation of ERK1/2 was assessed by Western blot analysis. O 2 production was measured by isoluminol-enhanced luminometry. Imaging technique was employed to measure neutrophil [Ca2+]i in individual cells. Thermal injury caused marked upregulation of Lyn and ERK1/2 accompanying enhanced neutrophil O 2 production. Treatment of rats with PTK blocker (AG556) or MAPK blocker (AG1478) before burn injury caused complete inhibition of the respective kinase activation. Both AG556 and AG1478 produced an ∼66% inhibition in O 2 production. Treatment with diltiazem (DZ) produced an ∼37% inhibition of O 2 production without affecting Lyn or ERK1/2 activation with burn injury. Ca2+mobilization was upregulated with burn injury but not affected by treatment of burn rats with AG556. Unlike the partial inhibition of burn-induced O 2 production by AG556, AG1478, or DZ, platelet-activating factor antagonist (PAFa) treatment of burn rats produced near complete inhibition of O 2 production. PAFa treatment also blocked activation of Lyn. The findings suggest that the near complete inhibition of O 2 production by PAFa was a result of blockade of PTK as well as Ca2+signaling. Overall, our studies show that enhanced neutrophil O 2 production after thermal injury is a result of potentiation of Ca2+-linked and -independent signaling triggered by inflammatory agents such as PAF.

  • burn
  • rat
  • polymorphonuclear neutrophil
  • protein kinase C signaling
  • platelet-activating factor blockade
  • Lyn blockade
  • extracellular signal-regulated kinase 1/2 blockade


  • This work was supported by National Institutes of Health Grants GM-53235 and GM-56865 (to M. M. Sayeed) and R21-AA-12901-01A1 (to M. A. Choudhry).

  • Address for reprint requests and other correspondence: M. M. Sayeed, Dept. of Surgery, Loyola Univ. Chicago Medical Center, 2160 South First Ave., Maywood, IL 60153 (E-mail:msayeed{at}

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • June 20, 2002;10.1152/ajpcell.00114.2002

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