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Effects of inhaled eotaxin on airway function and inflammatory cell influx in sensitized and non-sensitized guinea pigs

Smith, Nicola and Johnson, Frederick J. 2006. Effects of inhaled eotaxin on airway function and inflammatory cell influx in sensitized and non-sensitized guinea pigs. Pulmonary Pharmacology and Therapeutics 19 (6) , pp. 391-396. 10.1016/j.pupt.20005.10.001

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Abstract

Eotaxin is a chemokine that has high potency and selectivity as a chemoattractant agent for eosinophils, signalling exclusively through the CCR3 receptor. Eotaxin is upregulated in the lungs within 3 h of antigen challenge, levels peak at 6 h in lung tissue and bronchoalveolar (BAL) fluid, and fall within 12 h of exposure. This study aimed to look at the effect(s) of eotaxin inhalation on airway function in guinea pigs, to determine if the expected inflammatory cell (eosinophil) infiltration could induce airway hyperreactivity (AHR) and a bronchoconstrictor response equivalent to the late asthmatic response (LAR) seen after antigen challenge. Animals were sensitised with 100 microg/ml OA with a dose on days 1 and 5. Airway responses to inhaled eotaxin (10 or 20 microg/ml) were determined by whole body plethysmography as the change in specific airway conductance (sGaw). Inhaled histamine (1mM) was used to investigate AHR, and cell influx was determined by BAL. Senitised animals exposed to 10 microg/ml eotaxin did not reveal a bronchoconstrictor response or AHR and cellular infiltration to the lungs was not evident 24 h after exposure. Both sensitised and non-sensitised animals exposed to 20 microg/ml eotaxin however revealed a significant bronchoconstrictor response 6h post-challenge, with reductions in sGaw of -27.0+/-6.6% and -32.3+/-6.8%, respectively. Both groups also displayed a bronchoconstrictor response to inhaled histamine 24h after exposure, indicating AHR, and a significant increase in both total and differential cell counts. Sensitised animals, however, revealed a significant increase in cell influx compared to non-sensitised animals. Nebulised eotaxin can reveal a LAR, AHR to inhaled histamine, and cellular infiltration to the lungs, possibly via the mobilisation of eosinophils from the bone marrow, and their subsequent recruitment to the airways.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Administration; Inhalation; Airway Resistance; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cell Count; Chemokine CCL11; Chemokines; CC Data Interpretation; Statistical Guinea Pigs; Histamine; Hypersensitivity; Inflammation; Male;Ovalbumin; Plethysmography; Whole Body; Respiratory Physiological Phenomena
ISSN: 1094-5539
Last Modified: 22 Feb 2013 03:10
URI: https://orca.cardiff.ac.uk/id/eprint/15439

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