Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4.

AUTOR(ES)

Dahlén, S E

RESUMO

The leukotrienes C4, D4, and E4, previously referred to as slow reacting substance of anaphylaxis, elicited long-lasting contractions of bronchi isolated from two birch pollen-sensitive asthmatics. The leukotrienes were 1,000 times more potent on a molar basis than was histamine or prostaglandin F2 alpha. Moreover, allergen released leukotrienes C4, D4, and E4 from the lung tissue of the asthmatics in amounts that appeared to correlate well to the anaphylactic bronchial contraction. Irrespectively of whether the lung was stimulated with specific allergen, the ionophore A23187 or 14C-labeled arachidonic acid, 15-hydroxyicosatetraenoic acid, and other lipoxygenase-derived monohydroxy acids were the major metabolites of arachidonic acid in the lung, and thromboxane A2 and prostaglandin I2 were the predominant cyclooxygenase products identified. However, cyclooxygenase inhibition with indomethacin had no effect on the contraction response to antigen in the bronchi, whereas, in the presence of U-60257, an inhibitor of leukotriene biosynthesis, the allergen neither released leukotrienes from the lung nor caused bronchial contraction. These findings indicate that leukotrienes C4, D4, and E4 are major mediators of allergic bronchoconstriction in man.

Documentos Relacionados

• Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects.
• The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics
• Level of complement activity and components C1, C4, C2, and C3 in complement response to bacterial challenge in malnourished rats.
• Changes in bronchial responsiveness to histamine at intervals after allergen challenge.
• Kinetic Properties of Phosphoenolpyruvate Carboxylase from C3, C4, and C3-C4 Intermediate Species of Flaveria (Asteraceae) 1