Plasma 9alpha,11beta-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma

Thorax. 2004 Jun;59(6):459-64. doi: 10.1136/thx.2003.013573.

Abstract

Background: Prostaglandin D(2) (PGD(2)) is a major cyclooxygenase product generated by activated mast cells during an allergic response. Assessment of PGD(2) and its metabolites in patients with asthma has mostly been performed in urine, bronchoalveolar lavage fluid and induced sputum, whereas human plasma determinations have been performed only sporadically.

Methods: In 32 patients with allergic asthma and 50 healthy non-allergic controls, baseline plasma and urinary levels of 9alpha,11beta-PGF(2), a primary PGD(2) metabolite, were assessed by gas chromatography/mass spectrometry. Serum tryptase levels were measured by fluoroenzyme immunoassay and urinary leukotriene E(4) (LTE(4)) by ELISA. In a subgroup of 10 asthmatics (randomly selected from the 32 study patients) in whom bronchial allergen challenges with specific allergens (Dermatophagoides pteronyssinus, n = 4, mixed grass pollens, n = 6) were carried out, measurements were taken both before and after provocation.

Results: At baseline no significant differences between mean plasma and urinary levels of the PGD(2) metabolite and serum tryptase levels were found in asthmatics or controls. Asthmatic patients had significantly higher urinary LTE(4) levels. Allergen challenge resulted in a significant early increase in the mean plasma 9alpha,11beta-PGF(2) level and only a borderline but significant increase in the urinary 9alpha,11beta-PGF(2) level within 2 hours after provocation. The challenge did not produce statistically significant changes in serum tryptase levels. Urinary LTE(4) levels remained significantly increased 4 hours after provocation.

Conclusions: PGD(2) is actively involved in the early asthmatic response to allergens. Measurement of 9alpha,11beta-PGF(2) release into plasma rather than urine following allergen challenge is a sensitive marker of enhanced PGD(2) synthesis, most probably due to mast cell activation.

MeSH terms

  • Adolescent
  • Adult
  • Allergens / physiology*
  • Asthma / metabolism*
  • Biomarkers / blood
  • Dinoprost / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Leukotriene E4 / urine
  • Male
  • Mast Cells / physiology*
  • Prostaglandin D2 / metabolism*
  • Serine Endopeptidases / blood
  • Time Factors
  • Tryptases

Substances

  • Allergens
  • Biomarkers
  • Leukotriene E4
  • Dinoprost
  • Serine Endopeptidases
  • Tryptases
  • Prostaglandin D2