Increased urinary excretion of the prostaglandin D2 metabolite 9α,11β-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction☆,☆☆,★,★★
Section snippets
Materials
Synthetic PGD2, PGF2α, 8-epi-PGF2α, 11-dehydro-thromboxane B2 and 13,14-dihydro-15-keto-PGF2α were obtained from Cayman Chemical Company (Ann Arbor, Mich.). Tritiated PGF2α ([5,6,8,9,11,12,14,15-3H]PGF2α, 168 Ci/mmol) was purchased from New England Nuclear (Boston, Mass.). Stock solutions of histamine diphosphate for the bronchoprovocations were prepared under good laboratory practice conditions by the hospital pharmacy and kept in the refrigerator until use. Crystalline lysine aspirin
Characteristics of the EIA for 9α,11β-PGF2
The specificity of the 9α,11β-PGF2 antibody was assessed in a series of cross-reactivity studies (Table I). The antibody proved to be highly specific for 9α,11β-PGF2, and neither PGF2α nor 8-epi-PGF2α caused any significant displacement of the tracer. The accuracy of the EIA for 9α,11β-PGF2 was assessed in both buffer and urine and was excellent (r2 = 0.99) (Fig. 1). The EIA was linear from 15.6 up to 200 pg/ml (Fig. 1). Samples exceeding this concentration were subsequently diluted to ensure
DISCUSSION
It is known that PGD2 is released in disorders involving mast cell activation, such as mastocytosis,21 but also in association with bronchoconstriction after allergen challenge in patients with atopic asthma. The levels of PGD2 in bronchoalveolar lavage fluid were found to be significantly increased after inhalation of 29 or endobronchial challenge with allergen.30 Furthermore, a recent study showed increases in the levels of PGD2, as well as its metabolite 9α,11β-PGF2, in bronchoalveolar
Acknowledgements
We thank the nurses, Heléne Blomqvist and Christina Larsson, at the Asthma and Allergy Research Unit, Division of Thoracic Medicine, Department of Internal Medicine, Karolinska Hospital and the technicians, Fatima Stensvad and Lilian Larsson, at the Department of Physiology and Pharmacology for excellent and dedicated assistance.
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2019, Seminars in ImmunologyCitation Excerpt :Prostaglandins D2 (PGD2) and metabolites (11 β prostaglandin F2α) are released by lung mast cells and are major product of cyclooxygenase pathway that causes bronchoconstriction and vasodilation in the airways. Increased urinary PGD2 and 11βPGF2 were seen in asthmatic patients undergoing allergen or aspirin challenges [69]. The utility of these urinary biomarkers is limited to research and deserve further evaluation especially with the development of novel therapies that target PGD2 receptors (DP2 antagonists).
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From aInstitute of Environmental Medicine, Karolinska Institutet; and the Departments of bMedical Biochemistry and Biophysics, cMedicine, and dPhysiology and Pharmacology at Karolinska Hospital, Stockholm.
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Supported by grants from the Swedish Medical Research Council (projects 14X-09071, 03X-217), the Swedish Association Against Asthma and Allergy (RmA), the Swedish Heart Lung Foundation, the Swedish Society of Medicine, Stiftelsen Lars Hiertas minne, the Institute of Environmental Medicine, the Swedish Environmental Protection Board (312049), and Karolinska Institutet.
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Reprint requests: Siobhán O’Sullivan, Asthma and Allergy Research Group, Institute of Environmental Medicine, Karolinska Institutet, S-171 77, Stockholm, Sweden.
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