Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury.
Leukotrienes, especially leukotriene B4, are important modulators of various neutrophil functions including adherence and chemotaxis. In previous work, we demonstrated that neutrophil adherence to extracellular matrixes was diminished in the acute stages of burn injury. In this study, we demonstrated that neutrophil adhesion to human and bovine endothelium in the baseline state and after stimulation with leukotriene B4 is depressed markedly after burn injury. The defect in stimulated adherence to endothelium was not specific to leukotriene B4 because impaired adhesion was observed with n-formyl-methionyl-leucyl-phenylalanine and ionophore A23187 as well. Moreover, the adherence defect correlated with 95% and 81% decreases in the release of leukotriene B4 and 5-hydroxy-(6E,87,117,147)-eicosatetraenoic acid, respectively, from burn PMN treated with A23187. Burn neutrophils also released proportionately more byproducts of leukotriene B4 omega oxidation, particularly 20-COOH-leukotriene B4, than did control neutrophils. When examined 3 1/2 weeks after injury, abnormalities in neutrophil leukotriene B4 generation and the adherence of burn neutrophils had recovered to near normal values. To determine whether the decreased release of leukotriene B4 from burn neutrophils was due to increased degradation or diminished synthesis of leukotriene B4, we examined the degradation of exogenous tritiated leukotriene B4 as well as the production of leukotriene B4 from tritiated arachidonic acid in neutrophils. Burn neutrophils converted significantly greater quantities of tritiated leukotriene B4 to tritiated 20-COOH-leukotriene B4 and synthesized markedly less tritiated leukotriene B4 from tritiated arachidonic acid than did control neutrophils, suggesting that decreased leukotriene B4 release by burn neutrophils was the result of both enhanced degradation and decreased synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Case Western Reserve University School of Medicine, MetroHealth Medical Center/Metropolitan General Hospital, Cleveland, OH 44109-1998.
B
B
Damtew
J A
JA
Marino
R B
RB
Fratianne
P J
PJ
Spagnuolo
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D002056:Burns / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology*
D007975:Leukotriene B4; D016718:Arachidonic Acid; D008084:Lipoxygenase