Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following
ischemia/reperfusion. It has been suggested that
leukotriene B4 may be released during
ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a)
leukotriene B4 is produced in the gut mucosa during
ischemia and reperfusion, and (b) inhibition of
leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of
ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline,
ischemia at 3 hours and reperfusion at 1 hour.
Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated
myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal
leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal
leukotriene B4 was entirely prevented by pretreatment with either
nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent
lipoxygenase inhibitors. Both
lipoxygenase inhibitors, as well as
leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that
leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel.