Neutrophil lipoxygenase activation and leukosequestration in postischemic myocutaneous flaps: role of LTB4
Kirschner, R.E.; Chiao, J.J.; Fyfe, B.S.; Hoffman, L.A.; Davis, J.M.; Fantini, G.A.
American Journal of Physiology 268(6 Pt 2): H2167-H2174
1995
ISSN/ISBN: 0002-9513 PMID: 7611467 Document Number: 442789
Reperfusion of ischemic tissues leads to eicosanoid- and polymorphonuclear leukocyte (PMN)-dependent injury. The present experiments were undertaken to examine the effect of myocutaneous flap ischemia-reperfusion on neutrophil 5-lipoxygenase activity and to define the role of leukotriene B-4 (LTB-4) in postischemic PMN infiltration into such composite tissue grafts. Anesthetized Yorkshire pigs underwent 6 h of rectus abdominis myocutaneous flap ischemia or sham ischemia, and LTB-4 generation was measured in calcium ionophore-stimulated neutrophils isolated from the circulation. At 30 min of reperfusion, neutrophil generation of LTB-4 increased from a baseline value of 31.0 +- 6.8 to 98.5 +- 5.1 ng/5 times 10-6 PMN (P lt 0.01) and was significantly greater than those neutrophils isolated from animals subjected to sham ischemia and reperfusion (54.3 +- 4.1 ng/5 times 10-6 PMN; P lt 0.01). Pretreatment of animals with the LTB-4-receptor antagonist, SC-41930 (n = 5), significantly attenuated reperfusion-associated 5-lipoxygenase activation (60.3 +- 11.6 ng LTB-4/5 times 10-6 PMN; P lt 0.01), suggesting the presence of a positive feedback mechanism for eicosanoid biosynthesis. Graft ischemia in control animals was associated with progressive PMN infiltration at 1 and 4 h of reperfusion (334 +- 92 and 667.2 +- 198 PMNs/25 high-powered fields, respectively); however, pretreatment with SC-41930 or the 5-lipoxygenase inhibitor, diethylcarbamazine, dramatically reduced PMN infiltration at 1 h of reperfusion (22 +- 3 and 64 +- 36 PMNs/25 high-powered fields, respectively; P lt 0.01) and at 4 h of reperfusion (178 +- 31 and 156 +- 40 PMNs/25 high-powered fields; P lt 0.01). These data indicate that myocutaneous flap ischemia-reperfusion leads to activation of 5-lipoxygenase in circulating PMNs and suggest that LTB-4 plays a critical role in the pathogenesis of reperfusion injury by amplifying the process of neutrophil recruitment into postischemic tissues.