Mediators of anaphylaxis but not activated neutrophils augment cholinergicresponses of equine small airways

Neutrophilic inflammation in small airways (SA) and bronchospasm mediated v ia muscarinic receptors are features of chronic obstructive pulmonary disea se in horses (COPD). Histamine, serotonin, and leukotrienes (LTs) are repor ted to be involved in the exacerbation of COPD and currently, histamine has been shown to increase tension response to electrical field simulation (EF S) in equine SA. We tested the effects of these mediators and the effects o f activated neutrophils on the cholinergic responses in SA. Histamine, sero tonin, and LTD4 had a synergistic effect on EFS responses and only an addit ive effect on the tension response to exogenous ACh or methacholine. Atropi ne and TTX entirely eliminated the EFS-induced tension response in the pres ence of all three inflammatory mediators, indicating that augmentation of t he EFS response applies only to the endogenous cholinergic response. Neutro phils isolated from control and COPD-affected horses were activated by zymo san, producing 18.1 +/- 2.3 and 25.0 +/- 2.3 nmol superoxide . 10(6) cells( -1) . 30 min(-1), respectively. However in contrast to the profound effect of mediators, incubation of SA for over 1 h in a suspension of up to 30 X 1 0(6) zymosan-treated neutrophils/ml did not significantly affect EFS respon ses of SA isolated from either control or COPD-affected horses. We conclude that in equine SA 1) the endogenous cholinergic responses are subject to s trong facilitation by inflammatory mediators; 2) activated neutrophils do n ot affect cholinergic responses in SA; and 3) in acute bouts of equine COPD , histamine, LTD4, and serotonin (mediators primarily associated with type I allergic reaction) rather than mediators derived from neutrophils most li kely contribute to increased cholinergic airway tone.