Recombinant human C5a-induced bronchoconstriction in the guinea pig: inhibition by an H1 antagonist after depletion of circulating granulocytes and platelets.
Recombinant human C5a (rHuC5a) causes an intense bronchoconstriction very quickly after i.v. injection into the guinea pig. In addition, it causes a biphasic blood pressure response characterized by a small hypotensive phase followed by a larger transient hypertensive phase. The overall goal was to determine the role of circulating cells in the bronchoconstriction and changes in blood pressure induced by rHuC5a. Intravenous injection of rHuC5a causes a transient granulocytopenia and thrombocytopenia, suggesting that these cells may be important targets of C5a action. However, the magnitude of granulocytopenia does not directly correlate with the magnitude of the bronchoconstriction, suggesting no direct connection between the events. Our studies continued to determine if depletion of circulating granulocytes and/or platelets altered the magnitude of, or the participation of histamine in, C5a-induced bronchoconstriction in the guinea pig. Selective depletion of circulating granulocytes, circulating platelets or both with specific antisera did not alter the severity, time of onset or duration of the rHuC5a-induced bronchoconstriction. The rHuC5a-induced hypertensive blood pressure response was significantly reduced only in guinea pigs depleted of just granulocytes. After depletion of both circulating granulocytes and platelets, histamine plays an important role in mediating the rHuC5a-induced bronchoconstriction as evidenced by the effectiveness of an H1 antagonist in inhibiting the response. This is in contrast to the ineffectiveness of the same H1 antagonist in inhibiting rHuC5a-induced bronchoconstriction in guinea pigs with normal numbers of circulating granulocytes and platelets or guinea pigs depleted of granulocytes only or platelets only.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Minnesota-Duluth.
D G
DG
Fraser
J F
JF
Regal
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D015936:Complement C5a / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006098:Granulocytes / Q000502:physiology*; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D015936:Complement C5a; D006632:Histamine; D011451:Prostaglandin-Endoperoxide Synthases; D011738:Pyrilamine