On the role of PGD2 metabolites as markers of mast cell activation in asthma

摘要: Prostaglandin D2 (PGD2) is the major cyclooxygenase metabolite of arachidonic acid released after stimulation mast cells. Quantification metabolites PGD2 can be used as an objective indices production and hence cell activation in vivo. The aim this thesis was to investigate feasibility measuring primary urinary PGD2, 9 alpha,11 beta-PGF2 with enzyme immunoassay (EIA). Measurements urine made by EIA were compared values obtained negative ion chemical ionisation gas chromatography-mass spectrometry (NCI GC-MS), gold standard method. Levels beta-PGF2, samples measured NCI GC-MS consistently lower than those EIA. analysis revealed presence two additional dinor compounds, shorter urine. One compounds identical beta-2,3-dinor-PGF2 which generated beta-oxidation identified electron impact (EI GC-MS). Thus, concentrations represent sum three metabolites. For convenience sake, are collectively referred subsequent studies. A 3-fold increase excretion documented allergen-induced bronchoconstriction nine atopic asthmatics. This challenge considered a positive control since it unambiguous that occurs during early phase airway obstruction. Histamine-induced did not result levels demonstrating formed consequence per se. Moreover, bronchial lysine-aspirin eight aspirin-intolerant asthmatics elicited accompanied significant beta-PGF2. Challenge higher dose aspirin produced even greater levels, indicating dose-dependent release aspirin-induced bronchoconstriction. pattern mediator (EAR) late asthmatic response (LAR) allergen investigated subjecting twelve mild challenge. Within one hour maximal bronchoconstrictor response, there markers, N tau-methylhistamine, histamine, end product cysteinyl-leukotrienes, leukotriene (LT)E4. all mediators also significantly elevated above baseline LAR. Urinary eosinophil protein X (EPX), marker activation, remained unaltered both EAR Preliminary evidence suggests diurnal variation EPX. Increased fluid osmolarity airways exercise, has been suggested trigger subset Twelve subjects history exercise-induced (EIB), exercised on stationary bicycle ergometer for 5 minutes. Seven (responders) experienced bronchoconstriction, whereas, pulmonary function remaining five (non-responders) stable. responder group increased non-responders at 30 90 minutes exercise. LTE4 tau-methylhistamine different between groups either time point although tendency group. (ABSTRACT TRUNCATED)