Mediators of anaphylaxis but not activated neutrophils augment cholinergic responses of equine small airways

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 276; no. 3; pp. 522 - L529
• Main Authors: Olszewski, Michal A, Robinson, N. Edward, Zhu, Feng-Xia, Zhang, Xiang-Yang, Tithof, Patricia K
• Format: Journal Article
• Language: English
• Published: United States 01.03.1999
• Subjects: Anaphylaxis - etiology; Animals; Cholinergic Fibers - physiology; Female; Histamine - pharmacology; Horse Diseases - physiopathology; Horses - physiology; Inflammation Mediators - physiology; Leukotriene D4 - pharmacology; Lung Diseases, Obstructive - veterinary; Male; Neutrophil Activation - physiology; Neutrophils - physiology; Respiratory System - innervation; Serotonin - pharmacology
• ISSN: 1040-0605; 0002-9513; 1522-1504
• DOI: 10.1152/ajplung.1999.276.3.L522

1  Department of Large Animal Clinical Sciences and 2  Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824 Neutrophilic inflammation in small airways (SA) and bronchospasm mediated via muscarinic receptors are features of chronic obstructive pulmonary disease in horses (COPD). Histamine, serotonin, and leukotrienes (LTs) are reported to be involved in the exacerbation of COPD, and currently, histamine has been shown to increase tension response to electrical field simulation (EFS) in equine SA. We tested the effects of these mediators and the effects of activated neutrophils on the cholinergic responses in SA. Histamine, serotonin, and LTD 4 had a synergistic effect on EFS responses and only an additive effect on the tension response to exogenous ACh or methacholine. Atropine and TTX entirely eliminated the EFS-induced tension response in the presence of all three inflammatory mediators, indicating that augmentation of the EFS response applies only to the endogenous cholinergic response. Neutrophils isolated from control and COPD-affected horses were activated by zymosan, 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 × 10 6 zymosan-treated neutrophils/ml did not significantly affect EFS responses of SA isolated from either control or COPD-affected horses. We conclude that in equine SA 1 ) the endogenous cholinergic responses are subject to strong facilitation by inflammatory mediators; 2 ) activated neutrophils do not affect cholinergic responses in SA; and 3 ) in acute bouts of equine COPD, histamine, LTD 4 , and serotonin (mediators primarily associated with type I allergic reaction) rather than mediators derived from neutrophils most likely contribute to increased cholinergic airway tone. airway smooth muscle; chronic obstructive pulmonary disease; inflammatory mediators; neutrophil activation; zymosan