AIRWAY RESPONSES IN VITRO FOLLOWING C_5A DES ARG‐INDUCED HYPER‐RESPONSIVENESS IN VIVO IN RABBITS

Abstract

The mechanism of C5a des Arg-induced airway hyper-responsiveness in rabbits was investigated. Airway smooth muscle from rabbits which had been pretreated in vivo, was studied in vitro. Tracheal rings, segmental bronchial rings, subsegmental bronchial spirals and lung parenchymal strips were all prepared from each rabbit lung. Although C5a des Arg produces hyper-responsiveness to histamine in vivo, which is inhibited by indomethacin, the airway smooth muscle responses in vitro from control, C5a des Arg and C5a des Arg plus indomethacin pretreated rabbits did not differ. The neutrophil counts in the tracheal and subsegmental bronchial specimens were increased in the C5a des Arg-treated group. Indomethacin significantly (P less than 0.05) inhibited the neutrophil influx in the subsegmental bronchi. It is concluded that intrinsic smooth muscle function is unaltered following C5a des Arg-induced hyper-responsiveness in vivo.

Complement Activation and C3 Allotype Distribution in Patients with Bronchial Asthma

“…Inflammation is thought to play a major role in bron chial asthma, underlying latc-phasc reaction and airway hyperresponsiveness [22], Airway hyperreactivity has been induced in rabbits by the application of the complement fragment C5adcsArg [23,24]. Several clinical studies point to the involvement of complement in the pathogenesis of asthma [9][10][11][24][25][26][27][28].…”

An unexpected role for the anaphylatoxin C5a receptor in allergic sensitization

“…Second, these components can induce smooth muscle contraction, mucus secretion, increased microvascular permeability, leukocyte migration and activation, and degranulation of some types of mast cells, thus mimicking some essential features of asthma (10). Third, and most important, neutralization of anaphylatoxin activity through the use of blocking antibodies or genetic targeting of various complement factors or their receptors has been shown to attenuate allergic inflammation and AHR in mice and guinea pigs (7,(11)(12)(13).…”