Possible changes in the leukocyte membrane as a mechanism of leukocyte adhesion to the venular walls induced by leukotriene B4 and fMLP in the microvasculature of the hamster cheek pouch.
Images of the microvasculature of the hamster cheek pouch were projected on TV monitor screen using a monochrome TV camera. Rolling and adhesion of the polymorphonuclear leukocytes on the venular wall were continuously recorded by a newly developed videodensitometer, as changes in average intensity of videosignals in a given detection window superimposed on the screen. Topical application (2.5, 5 and 10 nmol/50 microliter) of fMLP (formyl-methionyl-leucyl-phenylalanine) or superfusion of leukotriene (LT) B4 (0.3, 3 and 30 pmol/ml/min) caused dose-dependent increase in the number of leukocytes adhering to the venules, but a tendency of rolling leukocyte to decrease. Local pretreatment of the microvasculature with a selective 5-lipoxygenase inhibitor (AA-1777) prevented the leukocyte adhesion induced by fMLP (10 nmol/50 microliter), indicating that this adhesion was induced through generation of 5-lipoxygenase products. Selective injection of fMLP (10, 30 and 100 pmol/0.1 microliter) by micropipette into the connective tissue close to the capillary dose-dependently increased the number of leukocytes adhering to the venule downstream, but injection of the highest dose (100 pmol/0.1 microliter) close to the venular wall caused no adhesion to the same venule. Similar results were obtained with LTB4 (30 fmol/0.1 microliter). These findings suggest that fMLP or LTB4 applied topically is absorbed from the capillaries and induces membrane changes in the leukocytes, but not in the endothelial cells, resulting in their adhesion to the venular wall.
Nagai
K
K
Department of Pharmacology, Kitasato University School of Medicine, Japan.
Katori
M
M
D000818:Animals; D016227:Benzoquinones; D002196:Capillaries / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000032:analysis / Q000187:drug effects; D002610:Cheek / Q000098:blood supply*; D002630:Chemotactic Factors / Q000494:pharmacology; D006224:Cricetinae; D007975:Leukotriene B4 / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology; D013499:Surface Properties; D014699:Venules / Q000187:drug effects; D014741:Video Recording
D016227:Benzoquinones; D002630:Chemotactic Factors; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C050196:AA 1777