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Neutrophil lipoxygenase activation and leukosequestration in postischemic myocutaneous flaps: role of LTB4
R E Kirschner1, J J Chiao, B S Fyfe
1Department of Surgery, New York Hospital and Cornell University Medical College 10021, USA.
Abstract:
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 B4 (LTB4) 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 LTB4 generation was measured in calcium ionophore-stimulated neutrophils isolated from the circulation. At 30 min of reperfusion, neutrophil generation of LTB4 increased from a baseline value of 31.0 +/- 6.8 to 98.5 +/- 5.1 ng/5 x 10(6) PMN (P < 0.01) and was significantly greater than those neutrophils isolated from animals subjected to sham ischemia and reperfusion (54.3 +/- 4.1 ng/5 x 10(6) PMN; P < 0.01). Pretreatment of animals with the LTB4-receptor antagonist, SC-41930 (n = 5), significantly attenuated reperfusion-associated 5-lipoxygenase activation (60.3 +/- 11.6 ng LTB4/5 x 10(6) PMN; P < 0.01), suggesting the presence of a positive feedback mechanism for eicosanoid biosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Ischemia-reperfusion injury increases neutrophil leukotriene B4 (LTB4) generation, a key mediator in polymorphonuclear leukocyte (PMN) infiltration. Blocking LTB4 receptors reduces this inflammatory response in myocutaneous flaps.
Area of Science:
- Inflammation and Immunology
- Vascular Surgery
- Biochemistry
Background:
- Ischemia-reperfusion (I-R) injury involves eicosanoids and polymorphonuclear leukocytes (PMNs).
- Understanding the role of leukotriene B4 (LTB4) in postischemic PMN infiltration is crucial for mitigating tissue damage.
Purpose of the Study:
- To investigate the impact of myocutaneous flap ischemia-reperfusion on neutrophil 5-lipoxygenase activity.
- To determine the specific role of LTB4 in PMN infiltration following ischemia-reperfusion in composite tissue grafts.
Main Methods:
- Yorkshire pigs underwent 6-hour rectus abdominis myocutaneous flap ischemia or sham procedures.
- LTB4 generation was quantified in neutrophils stimulated with calcium ionophore.
- The effect of an LTB4-receptor antagonist (SC-41930) on LTB4 production was assessed.
Main Results:
- Neutrophil LTB4 generation significantly increased after 30 minutes of reperfusion compared to baseline and sham groups.
- Pretreatment with the LTB4-receptor antagonist SC-41930 markedly reduced reperfusion-associated 5-lipoxygenase activation.
- These findings suggest a positive feedback loop in eicosanoid biosynthesis during reperfusion injury.
Conclusions:
- Ischemia-reperfusion significantly elevates neutrophil LTB4 generation.
- LTB4 plays a critical role in mediating PMN infiltration into ischemic-reperfused myocutaneous flaps.
- Targeting the LTB4 pathway may offer a therapeutic strategy to reduce inflammation and tissue damage in I-R injury.