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

On the role of PGD2 metabolites as markers of mast cell activation in asthma. Research Abstract Details 

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On the role of PGD2 metabolites as markers of mast cell activation in asthma. Abstract Text:

S O'Sullivan,

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

On the role of PGD2 metabolites as markers of mast cell activation in asthma. Publishing Authors By Initials

S O'Sullivan,

For similar cells: connective tissue cells: mast cells research abstracts see: cells: connective tissue cells: mast cells research

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On the role of PGD2 metabolites as markers of mast cell activation in asthma. Journal Published:

PUBLICATION TYPE: Review

Journal: Acta physiologica Scandinavica. Supplementum

VOLUME: 644

Page Numbers: 1-74

Journal Abbreviation:

ISSN: 0302-2994

DAY: 20

MONTH: Apr

YEAR: 1999

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

Number of References: 375

LANGUAGE: eng

NlmUniqueID: 376307

On the role of PGD2 metabolites as markers of mast cell activation in asthma. Keywords Mesh Terms:

KEYWORDS: Mast Cells

MESH TERMS: pathology

Chemical & Substance for Abstract: On the role of PGD2 metabolites as markers of mast cell activation in asthma. Information

Substance Name: Histamine

Registry Number: 51-45-6

Grant and Affiliation Information for On the role of PGD2 metabolites as markers of mast cell activation in asthma.

AFFILIATION: National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Country: ENGLAND

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MEDLINETA: Acta Physiol Scand Suppl

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