title: Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein.
abstract: The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n=14, p<0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1 ± 1% vs. 47 ± 6% evoked by 1 nM SP, n=14, p<0.001). Consistent with epithelial damage, PGE2 release in response to both acrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, p<0.01), as determined using ELISA. In contrast, exogenous PGE2 was 2.8-fold more potent in VIRUS relative to SHAM segments (-log EC50 7.82 ± 0.14 vs. 7.38 ± 0.05, n=7, p<0.01) whilst responses of VIRUS segments to the β-adrenoceptor agonist isoprenaline were similar to SHAM segments. In conclusion, relaxation responses evoked by acrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Esther Y
authors.initials: EY
authors.lastname: Cheah
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Mann
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Burcham
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA 6009, Australia. Electronic address: Peter.Henry@uwa.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Henry
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D009924:Organ Culture Techniques; D009976:Orthomyxoviridae Infections; D014132:Trachea / Q000187:drug effects* / Q000502:physiology / Q000821:virology
chemical_list: D000171:Acrolein
keywords: Acrolein; Airway epithelium; Influenza A; Mouse tracheal smooth muscle; Relaxation