Contractile effect of anaphylatoxin C5a and of a mimetic peptide on the human umbilical artery: further evidence for leukocyte-dependent vasomotion.
Reproducible and concentration-dependent contractile effects were recorded when the human umbilical artery was exposed to recombinant C5a (>or=1 nM). The synthetic mimetic peptide Ac-YSFKPMPLaR was about 100-fold less potent in this respect, and its effect was largely prevented by treatment with the TP prostanoid receptor antagonist SQ 29548. The selective cyclooxygenase-1 inhibitor flurbiprofen, but not by the cyclooxygenase-2 inhibitor L-745337, prevented the contractile effect of both C5a and Ac-YSFKPMPLaR. Cells positive for C5a receptor (CD 88) immunoreactivity were scattered in the umbilical artery structure and were apparently more abundant in the periphery. The macrophage marker CD 68 was also expressed by dispersed cells, with a distribution similar to CD 88; both markers were co-expressed in some cells represented in consecutive sections. Immunoblot for C5a receptors has been applied to tissue or cells extracts: a specific approximately 42-kd major band observed in peripheral blood leukocytes was also expressed by the fresh umbilical artery, but not by cultured smooth muscle cells derived from the umbilical artery. Macrophages dispersed in the connective structure of the vessel wall may, in response to C5a receptor agonists, release prostanoids formed by cyclooxygenase-1 that indirectly contract smooth muscle cells. Leukocyte-dependent vasospasm may be relevant in situations in which complement is activated and may trigger thromboembolic complications via the secretion of thromboxane-like eicosanoids also active on circulatory platelets.
Fortin
Jean-Philippe
JP
Centre Hospitalier Universitaire de Québec, Centre de recherche du Pavillon l'Hôtel-Dieu de Québec, Québec, Canada.
Bouthillier
Johanne
J
St-Pierre
Serge A
SA
Marceau
François
F
D015703:Antigens, CD / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000187:drug effects; D014469:Umbilical Arteries; D014661:Vasoconstriction / Q000187:drug effects*
D015703:Antigens, CD; D016861:Cyclooxygenase Inhibitors; D007189:Indans; C093700:L 745337; D010455:Peptides; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D005480:Flurbiprofen; D015936:Complement C5a