6-ketoprostaglandin-f1-alpha and Bronchial-Spasm

To determine if platelet activation occurs after allergen inhalation in atopic asthmatics, we measured two urinary metabolites of the principal cyclooxygenase product of platelets, thromboxane A2 (TxA2), using the sensitive and specific technique of gas chromatography-negative ion, chemical ionization-mass spectrometry. Seven atopic asthmatics underwent allergen challenge after low dose aspirin to suppress platelet thromboxane generation and on placebo days. On placebo days, the urinary levels of 2,3-dinor-TxB2 increased from 76 +/- 22 pg/mg creatinine to 216 +/- 95 after allergen, and 11-dehydro-TxB2 from 396 +/- 98 to 627 +/- 137 (p less than 0.05). Low dose aspirin suppressed excretion of urinary thromboxane metabolites and prevented the rise after allergen inhalation without altering the bronchoconstriction. Excretion of 2,3-dinor-6-keto-PGF1 alpha, a metabolite of prostacyclin, was unaltered by this aspirin regimen. We conclude that platelets are activated after allergen challenge, but that platelet-derived TxA2 is not important in the early bronchoconstrictor response.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Allergens; Aspirin; Blood Platelets; Bronchial Spasm; Clinical Trials as Topic; Cyclooxygenase Inhibitors; Female; Forced Expiratory Volume; Gas Chromatography-Mass Spectrometry; Humans; Male; Placebos; Platelet Activation; Thromboxane A2; Thromboxane B2

In order to investigate whether bronchopulmonary hyperresponsiveness represents a unique property of sensitized lungs, we examined the responses of lungs from either actively sensitized, passively sensitized, or nonsensitized (control) guinea pigs to in vitro bronchoconstriction (BC) and release of thromboxane (TX) B2, 6-keto-PGF1 alpha, and histamine induced by platelet-activating factor (PAF-acether) or leukotriene (LT) D4. Guinea pigs were actively sensitized with 10 micrograms of either ovalbumin or Dermatophagoides farinae extract in AI(OH)3 injected intraperitoneally twice at a 2-wk interval. Seven days after the second injection (booster injection), the lungs were removed, ventilated, and perfused via the pulmonary artery with Krebs solution containing 2.5 g/L bovine serum albumin. In lungs from actively sensitized animals, BC was induced by significantly lower doses of PAF-acether and LTD4 than those required to elicit the same response in control preparations. In addition, sensitized lungs released more TxB2, 6-keto-PGF1 alpha, and histamine in response to PAF-acether and LTD4 than did control lungs. Increased mediator release was also observed upon challenge of lungs from actively sensitized animals with arachidonic acid and histamine. Lungs from guinea pigs passively sensitized with serum from actively sensitized animals did not exhibit increased responsiveness to PAF-acether as compared to control lungs. The hyperresponsiveness induced after booster injection of the antigen occurred concomitantly with an increase in the homocytotropic antibody titer (as measured by passive cutaneous anaphylaxis) and persisted for 3 months after sensitization, when the levels of circulating antibodies and lung response to antigen challenge returned to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchial Spasm; Capillary Permeability; Female; Guinea Pigs; Histamine; Immunization; Immunization, Secondary; Kinetics; Lung; Male; Ovalbumin; Perfusion; Platelet Activating Factor; Pulmonary Circulation; Respiratory Hypersensitivity; SRS-A; Thromboxane B2