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Airway reactivity, inflammatory cell influx and nitric oxide in guinea-pig airways after lipopolysaccharide inhalation

Toward, Toby J. and Broadley, Kenneth John 2000. Airway reactivity, inflammatory cell influx and nitric oxide in guinea-pig airways after lipopolysaccharide inhalation. British Journal of Pharmacology 131 (2) , pp. 271-281. 10.1038/sj.bjp.0703589

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Abstract

The aim of this study was to investigate the relationship between airway reactivity, leukocyte influx and nitric oxide (NO), in conscious guinea-pigs after aerosolized lipopolysaccharide (LPS) exposure. Inhaled histamine (1 mM, 20 s), causing no bronchoconstriction before LPS exposure (30 μg ml−1, 1 h), caused bronchoconstriction at 0.5 and 1 h (P<0.02) after LPS exposure. This airway hyperreactivity (AHR) recovered by 2 h. In contrast, 48 h after LPS exposure, the response from a previously bronchoconstrictor dose of histamine (3 mM, 20 s) was attenuated (P<0.01) i.e. airway hyporeactivity (AHOR). Investigation of the cellular content of bronchoalveolar lavage fluid (BALF) from these animals revealed a rapid (0.5 h: 691 fold increase) and progressive neutrophil influx after LPS exposure (24 h: 36.3±2.3×106 cells per sample), that subsided 48 h later. Macrophages and eosinophils also time-dependently increased (0.5 h: 4.6±0.4 and 0.1±0.05; 48 h: 31.0±6.0 and 1.8±0.3×106 cells per sample, respectively) after LPS, compared to vehicle exposure (24 h: neutrophils, eosinophils and macrophages: 0.28±0.19, 0.31±0.04 and 4.96±0.43×106 cells per sample, respectively). The combined NO metabolites in BALF, after vehicle (1 h), or LPS (1 h: AHR and 48 h: AHOR) exposure, were respectively increased (41%, P<0.01), decreased (47%, P<0.01) and further increased (80%, P<0.001), compared with naï ve animals. Inhaled No-nitro-L-arginine methyl ester (L-NAME: 1.2 and 12 mM, 15 min), reduced BALF NO metabolites 2 h later, but did not cause AHR to histamine (P>0.05). When L-NAME inhalation followed LPS, AHR was prolonged from 1 h to at least 4 h (P<0.01). In summary, aerosolized LPS inhalation caused neutrophil and macrophage airways infiltration, and an early development of AHR followed 48 h later by AHOR to histamine. AHR and AHOR coincided with a respective reduction and elevation in airways NO (metabolites). Thus, NO may aid recovery from AHR, as inhibition of its production prolongs AHR. However, NO deficiency alone is not responsible for LPS-induced AHR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Airway hyperreactivity; airway hyporeactivity; lipopolysaccharide; histamine; conscious guinea-pigs; leukocyte infiltration; nitric oxide; ω-nitro-L-arginine methyl ester
ISSN: 1476-5381
Last Modified: 04 Jun 2017 03:01
URI: http://orca.cf.ac.uk/id/eprint/15390

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