Technique for quantification of LTB4-induced changes in peripheral granulocyte counts in vivo in the rabbit.
A method to quantify leukotriene B4-(LTB4)-induced changes in peripheral granulocyte counts in the rabbit is described. Rabbits were surgically prepared with vascular access ports cannulating the right external jugular vein. This preparation made possible rapid, accurate, and repeated sampling of venous blood. Intravenous infusion of LTB4 (0.5-2 micrograms/mL) into the left marginal ear vein was found reproducibly to cause an initial, rapid (1-5 min) leukopenia (64%-100% reduction) followed by an extended (20-30 min) leukocytosis (121%-178% increase). Saline infusion for 30 min resulted in no changes in peripheral granulocyte number. The method described was sensitive and reproducible enough to allow evaluation of the LTB4 receptor antagonist, LY223982 (10 mg/kg, i.v.), which was shown to block both the leukopenia and the leukocytosis induced by LTB4 infusion.
Griswold
D E
DE
Department of Respiratory/Inflammation Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Martin
L
L
Ventre
J
J
Meunier
L
L
Perry
L
L
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D002404:Catheterization; D005260:Female; D006098:Granulocytes / Q000187:drug effects*; D007958:Leukocyte Count / Q000187:drug effects*; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects; D011817:Rabbits
D001577:Benzophenones; C065916:LY 223982; D007975:Leukotriene B4