title: Mast cell effector mechanisms.
abstract: Several lines of evidence support the central role of the cysteinyl leukotrienes in aspirin-sensitive asthma, although their cellular source is unknown. The two most likely cells are the mast cell and eosinophil. Compared with aspirin-tolerant patients with asthma, patients with aspirin-sensitive asthma have been found to have a greater infiltration of mast cells and eosinophils in bronchial biopsy samples, although proportions of activated eosinophils were similar. Findings that support the involvement of mast cells include elevated serum histamine and tryptase levels after aspirin challenge in sensitive subjects, in line with a decrease in lung function and increased histamine and leukotriene C4 levels in nasal secretions; release of high-molecular-weight neutrophil chemotactic factor into serum after challenge; and prevention of aspirin-induced bronchoconstriction by pretreatment with cromolyn sodium or nedocromil sodium. These agents are also effective in protecting against bronchoconstriction induced by hyperosmolar stimuli, a challenge that is not associated with increased leukotriene E4 responsiveness but that is followed by increased release of histamine and prostaglandin D2 into bronchoalveolar lavage fluid. Antihistamines are poorly effective at inhibiting aspirin-induced bronchoconstriction but have been shown to attenuate the bronchoconstrictor response to hyperosmolar challenge. The main effector mechanism in hyperosmolar-induced bronchoconstriction appears to be mast cell activation and histamine release.
authors.affiliation: Department of Allergy and Respiratory Medicine, Guy's Hospital, London, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lane
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced; D001250:Asthma, Exercise-Induced / Q000503:physiopathology; D006801:Humans; D008407:Mast Cells / Q000502:physiology*
chemical_list: D001241:Aspirin