Eicosanoids and platelet-activating factor in allergic respiratory diseases.
The nature of the lipid mediators released at an inflammatory site in the airways is dependent not only on the individual cells and inflammatory stimuli present but also on a complex interaction between neighboring cells and their lipid products. These lipid mediators share overlapping activities, and current research is directed toward determining the critical molecules involved in the pathogenesis of particular inflammatory states. How may the release of these lipid mediators play a role in the pathogenesis of asthma? Allergic persons after inhalation of specific allergen have a dual bronchospastic response. The early asthmatic response occurring shortly after allergen challenge is most likely secondary to the action of bronchoconstrictor molecules (e.g., LTC4, PGD2, PAF) released by human lung mast cells as a consequence of IgE-mediated degranulation. An inflammatory process than occurs in the airways that is characterized by an influx of eosinophils and neutrophils into the airway epithelium and bronchial fluids. This inflammatory response corresponds to the late asthmatic phase occurring several hours after allergen challenge. Release of sulfidopeptide leukotrienes, PAF, and cyclooxygenase products by cells infiltrating the airways may be involved in the bronchial smooth muscle constriction, mucosal edema, and mucus hypersecretion observed during these late asthmatic responses. In the future, the therapeutic use of specific antagonists of the biosynthetic enzymes of the 5-lipoxygenase pathway and receptor antagonists of the eicosanoids and PAF holds great promise for the modulation of airway inflammation.
Henderson
W R
WR
Department of Medicine, University of Washington, Seattle 98195.
D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D015777:Eicosanoids / Q000276:immunology*; D004804:Eosinophils; D006801:Humans; D015289:Leukotrienes / Q000276:immunology; D008264:Macrophages; D009504:Neutrophils; D010972:Platelet Activating Factor / Q000276:immunology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011453:Prostaglandins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000201:enzymology / Q000276:immunology*; D013931:Thromboxanes / Q000276:immunology
D015777:Eicosanoids; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011453:Prostaglandins; D013931:Thromboxanes; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases