Investigations into the mechanisms of late phase responses in guinea pig airways

Hutson, Penelope Ann (1989) Investigations into the mechanisms of late phase responses in guinea pig airways. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

This study describes a model of allergen-induced early and late responses in non-anaesthetised guinea pigs, sensitised and challenged by inhalation of ovalbumin. Sensitisation is associated with an eosinophilia in the lung and an increase in airways responsiveness in vivo and in vitro. Following challenge, three phases of airflow limitation are observed: an early response (EAR) within 5 minutes and peaking at 2 hours, a late response peaking at 17 hours (LAR) and a later period of airways obstruction at 72 hours. The late responses are associated with an influx of neutrophils and eosinophils into the airways which is inhibited by administration of the platelet activating factor (PAF) antagonists, WEB 2086 and WEB 2170, before challenge. This suggests that PAF release during the EAR is important for the cellular infiltration. Neutrophil depletion and manipulation with the anti-asthmatic drugs, sodium cromoglycate, nedocromil sodium and salbutamol suggests that, despite a temporal association between the neutrophil accumulation and airways obstruction at 17 hours, these events are not functionally related. Pharmacological manipulation reveals no clear relationship between airways obstruction and eosinophil accumulation. However, the fact that PAF antagonists administered after the EAR inhibit the late responses and later eosinophil accumulation, implicates PAF in these events. In conclusion, late responses in this model have distinct similarities to the LAR in humans and should provide a useful means of further investigating the pathogenesis of bronchial asthma. (DX88263)

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