Interaction of leukotrienes with other mediators in pathological models and its regulation by drags.

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1) NEUTROPHIL EXTRAVASATION: Vital microscopic analyses in microcirculation of hamster cheek pouch revealed that after topical application of leukotriene (LT) B_4 extravasated neutrophils by five steps. Adhesion on endothelial cells was initiated by membrane changes of neutrophils, occurred less than 4.5 sec after exposure of LTB_4 and was inhibited by an antibody against CD18, indicating that adhesion was induced not by newly synthesized protein, but by activation of adhesion molecules, CD_<11>/CD_<18>. Intra-arteriolar infusion of LTB_4 did not induce the adhesion, intra-venular infusion did it and the adhesion was inhibited by an antibody against ICAM-1, indicating that ICAM-1 is not induced in the tissue, but normally present in only venular endothelial cells.2) ETHANOL-INDUCED GASTRIC MUCOSAL INJURY: Vital microscopic observation of the submucosal microcirculation of rat stomach after exposure of the gastric mucosa to 30-50 % ethanol revealed that this injury was induced by constr … More iction of the collecting venules of the mucosa and subsequent congestion of the mucosal blood flow. LTC_4 was generated in the gastric wall after ethanol and exogenous LTC_4 applied on the mucosal microvasculature constricted the collecting venules. The mucosal type mast cells in the gastric mucosa were selectively stained by an antibody against 5-lipoxygenase. Substance P and CGRP were also increased in the gastric lumen after exposure to ethanol. Constriction of the collecting venules after ethanol was inhibited by pretreatment with capsaicin, but not by spantide, an old Substance P antagonist.3) AIRWAY RESISTANCE: Intravenous injection of LTC_4 and LTD_4 to guinea pigs increased airway resistance and secreted tissue kallikrein into the lumen of the respiratory tract with increased secretion. LTC_4 was more potent than LTD4. The kallikrein secretion was induced by release of thromboxane (TX) A_2 and acetylcholine successively. Bradykinin released by kallikrein formed a positive feed back loop for secretion of kallikrein by release of TXA_2 and acetylcholine. Less