Bradykinin-induced proinflammatory signaling mechanisms.
Intravital microscopic techniques were used to examine the mechanisms underlying bradykinin-induced leukocyte/endothelial cell adhesive interactions (LECA) and venular protein leakage (VPL) in single postcapillary venules of the rat mesentery. The effects of bradykinin superfusion to increase LECA and VPL were prevented by coincident topical application of either a bradykinin-B(2) receptor antagonist, a cell-permeant superoxide dismutase (SOD) mimetic or antioxidant, or inhibitors of cytochrome P-450 epoxygenase (CYPE) or protein kinase C (PKC) but not by concomitant treatment with either SOD, a mast cell stabilizer, or inhibitors of nitric oxide synthase, cyclooxygenase, xanthine oxidase, NADPH oxidase, or platelet-activating factor. Immunoneutralizing P-selectin or intercellular adhesion molecule-1 (ICAM-1) completely prevented bradykinin-induced leukocyte adhesion and emigration but did not affect VPL. On the other hand, stabilization of F-actin with phalloidin prevented bradykinin-induced leukocyte emigration and VPL but did not alter leukocyte adhesion. These data indicate that bradykinin induces LECA in rat mesenteric venules via a B(2)-receptor-initiated, CYPE-, oxidant- and PKC-mediated, P-selectin- and ICAM-1-dependent mechanism. Bradykinin also produced VPL, an effect that was initiated by stimulation of B(2) receptors and involved CYPE and PKC activation, oxidant generation, and cytoskeletal reorganization but was independent of leukocyte adherence and emigration.
Shigematsu
Sakuji
S
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130, USA.
Ishida
Shuji
S
Gute
Dean C
DC
Korthuis
Ronald J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008208:Lymphatic System / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D019007:P-Selectin / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects; D014741:Video Recording
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D004798:Enzymes; D019007:P-Selectin; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D018799:Intercellular Adhesion Molecule-1; D001920:Bradykinin