Induction of plasma exudation and inflammatory cell infiltration by leukotriene C4 and leukotriene B4 in mouse peritonitis.
Leukotriene induction of the fluid and cellular phases of the inflammatory response in the mouse was evaluated. Intraperitoneal injection of leukotriene C4 (LTC4 250 ng) led to dye extravasation but not polymorphonuclear leukocyte (PMN) infiltration, whereas injection of leukotriene B4 (LTB4 250 ng), led to PMN infiltration but not dye extravasation. The injection of both leukotrienes did not result in synergy. LTC4 did not appear to induce significant release or formation of chemotactic mediators, but the dye extravasation induced by LTC4 was inhibited by the vasoactive amine antagonist cyproheptadine and not by the eicosanoid inhibitors phenidone or naproxen. The response was markedly inhibited by the cytokine and eicosanoid inhibitors SK&F 86002 and SK&F 104493. PMN infiltration induced by LTB4 was not inhibited by SK&F 86002 or phenidone but was abrogated by colchicine treatment. LTB4 in this model did not appear to cause release or formation of vasoactive mediators. These leukotrienes appeared to be independent, complementary, and sufficient to mount a complete inflammatory response in the mouse.
Griswold
D E
DE
Department of Respiratory/Inflammation Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Webb
E F
EF
Hillegass
L M
LM
D000818:Animals; D001201:Ascites / Q000139:chemically induced; D002199:Capillary Permeability / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003078:Colchicine / Q000494:pharmacology; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology; D013189:SRS-A / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D013844:Thiazoles / Q000494:pharmacology
D007093:Imidazoles; D011720:Pyrazoles; D013189:SRS-A; D013844:Thiazoles; D007975:Leukotriene B4; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole; C015429:phenidone; D003078:Colchicine