Microvascular effects of anaphylatoxins C3a and C5a.
The direct microvascular effects of human C3a and C5a were investigated by using hamster cheek pouches prepared for intravital microscopy. Topical application of 10 nM C3a resulted in pronounced microcirculatory alterations, characterized by vasoconstriction, platelet aggregation, and an increase in macromolecular leakage at postcapillary venules, as assessed by extravasation of intravascular fluorescein-labeled dextran (m.w. 150,000). Exposure of the preparation to 500 nM COOH-terminal octapeptide analogs of C3a resulted in a microvascular response almost identical to that of C3a, supporting the view that the active site of this anaphylatoxin resided within the COOH-terminal portion. Changes similar to those caused by C3a were also induced by 20 or 100 nM C5a and, in addition, the higher concentration of C5a caused accumulation of polymorphonuclear leukocytes (PMNL) in small venules and somewhat prolonged vascular leakage from venules exhibiting PMNL accumulation. Histamine was found to partially mediate the vascular leakage induced by C3a and the initial (first 5 min) permeability response to the high concentration of C5a, whereas the subsequent leakage induced by the latter anaphylatoxin was unaffected by mepyramine pretreatment. In neutropenic and mepyramine-treated animals exposed to the high concentration of C5a, a partial reduction of both the early and the subsequent vascular leakage was seen, indicating that accumulated PMNL play a role in the prolonged phase of leakage. The pronounced microvascular alterations induced by low concentrations of C3a and C5a strengthen the view that these anaphylatoxins act as mediators of inflammatory reactions in which the complement system is activated.
D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D002610:Cheek / Q000098:blood supply; D003176:Complement C3 / Q000502:physiology*; D015926:Complement C3a; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a; D006224:Cricetinae; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology*; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation; D011738:Pyrilamine / Q000494:pharmacology; D014661:Vasoconstriction; D014699:Venules / Q000503:physiopathology
D003176:Complement C3; D003182:Complement C5; D009842:Oligopeptides; D015926:Complement C3a; D015936:Complement C5a; D006632:Histamine; D011738:Pyrilamine