PubMed · 471010
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M Kattan. 1979-09-20. Challenging the airways.. https://doi.org/10.1056/nejm197909203011217
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Collagen injected to guinea pigs i.v. increased the pulmonary resistance to inflation (bronchoconstriction) and induced thrombocytopenia. Immune platelet depletion protected against the effects of collagen, and has been shown not to prevent bronchoconstriction induced by the prostaglandin/thromboxane A2 precursor arachidonic acid. Use of inhibitors demonstrated that histamine, serotonin, acetylcholine and bradykinin were not involved with the effects of collagen in the guinea pig. Aspirin and indomethacin inhibited collagen-induced bronchoconstriction completely and thrombocytopenia partly, supporting the hypothesis that the former is prostaglandin cyclo-oxygenase dependent, whereas the latter has a thromboxane A2-independent mechanism as well. Carrageenan, heparin and reserpine inhibited the in vivo effects of collagen to various extents, but their precise mechanism of action could not be discovered. Collagen-induced bronchoconstriction is strictly platelet and thromboxane A2-dependent.
Because postmortem studies of humans provide little information on the initial pathophysiologic events in asthma, animal models have been developed. Recently the Ascaris-allergic rhesus monkey has provided an opportunity to examine the onset of pathophysiologic changes following challenge and to correlate them with airway structure. These studies have suggested that the initial interaction between antigen and mast cells may occur in the bronchial lumen or in the epithelium superficial to the tight junctions, where a small but significant percentage of airway mast cells exist. It also appears that this initial antigen-antibody interaction results in the release of mediators that both stimulate the rapidly adapting stretch receptors in the mucosa and alter the mucosal barrier so that proteins of large molecular weight can penetrate. The fact that antigen challenge results in hyperresponsiveness to a subsequent dose of inhaled histamine and increased systemic absorption of histamine suggests that the airway hyperresponsiveness could be related to increased penetration of histamine into the bronchial wall. These observations suggest that the initial event in an acute asthmatic attack is the release of mediators from superficial mast cells, and that this amplifies the allergic response by altering the mucosal permeability so that more antigen reaches the submucosal mast cells. This altered permeability may also help explain the hyperreactivity of the airways to nonspecific airway stimulants in persons with asthma.