Contractile Responses to Allergen and Cholinergic Stimulation in Bronchus and Trachea of Cockroach Allergen-Sensitized Guinea Pigs

Abstract

Airway hyperreactivity is a hallmark of asthma. Yet, the role of allergic sensitization in the hyperreactivity remains controversial. This study examined the effects of airborne cockroach allergen (CRa) sensitization on the contractility of bronchial (BSM) and tracheal (TSM) smooth muscle rings to cholinergic stimulations, and to specific antigen, in vitro. Guinea pigs were actively immunized with CRa, 5 mg (high dose, HD), 0.5 mg (low dose, LD), or saline aerosols (2 ×/day, 5 days/week, for 4 weeks) and challenged by CRa inhalation 5 days after last exposure. Twenty-four hours postchallenge, the contractions of the TSM and BSM to electrical field stimulation (EFS), acetylcholine (ACh), and to CRa were measured in vitro. In addition, the contraction to these stimuli were also examined in the passively sensitized TSM with the sera of CRa-immunized guinea pigs. The contractile responses of actively immunized and passively sensitized tissues to EFS and ACh were very similar to those of control tissues. CRa induced dose-dependent contractions in both actively immunized and passively sensitized, but not in control, tissues. The CRa-induced contraction was stronger in the HD group than in the LD group (p < 0.0001). Leukotriene C4/D4 receptor antagonist LY-171883 inhibited the CRa-induced contraction by 86% in actively immunized TSM, and by 9% in the passively sensitized TSM. Pyrilamine inhibited the contraction by 57% in actively immunized TSM and 70% in passively sensitized TSM. The results indicate that CRa sensitization does not cause increased airway smooth muscle contractility to cholinergic stimulations, but induces antigen-specific contractions in vitro. Leukotrienes appear to play a significant role in the CRa-specific contractions, more in the actively immunized than those in the passively sensitized tissues, while histamine exerts a moderate effect on the CRa-induced contractions.