Histamine induces leukocyte rolling in post-capillary venules. A P-selectin-mediated event.
The objective of this study was to systematically assess the molecular mechanisms and kinetics of histamine-induced leukocyte rolling in rat mesenteric venules using intravital microscopy. A complicating factor in these studies is surgical preparation-induced leukocyte rolling (spontaneous rolling), which leads to a lack of effect of histamine on this parameter. Therefore, we identified the source of the surgery-induced leukocyte rolling (partial mast cell degranulation) and established that pretreatment of animals with sodium cromoglycate (connective tissue mast cell stabilizer) inhibited spontaneous leukocyte rolling. Superfusion of the mast cell-stabilized rat mesentery with histamine caused a profound increase in leukocyte rolling which persisted for the entire hour of experimentation. Diphenhydramine (H1-receptor antagonist) but not cimetidine (H2-receptor antagonist) prevented the rise in histamine-induced leukocyte rolling. An anti-P-selectin Ab but not an anti-CD18 Ab reversed the histamine-induced leukocyte rolling in a dose-dependent fashion. In this model of low base line rolling, exposure of the mesentery to the chemotactic agent platelet-activating factor did not induce leukocyte rolling or adhesion. However, co-administration of histamine with platelet-activating factor did indeed promote leukocyte adhesion suggesting that the presence of at least one effector of P-selectin is a minimal requirement for chemotactically-stimulated leukocytes to adhere to postcapillary venules. This study demonstrates for the first time that histamine induces leukocyte rolling via a P-selectin-dependent mechanism in vivo. This is a prolonged, H1 receptor-mediated event that may contribute significantly to the early phase of inflammation.
Kubes
P
P
Immunological Sciences Research Group, University of Calgary Medical Center, Alberta, Canada.
Kanwar
S
S
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens; D002448:Cell Adhesion; D004205:Cromolyn Sodium / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D019007:P-Selectin; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000502:physiology; D013997:Time Factors; D014699:Venules / Q000166:cytology
D015703:Antigens, CD; D018821:CD18 Antigens; D019007:P-Selectin; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011969:Receptors, Histamine H1; D006632:Histamine; D004205:Cromolyn Sodium