Release of Prostaglandin D₂into Human Airways during Acute Antigen Challenge

Abstract

Among the many possible mediators of the early asthmatic response, prostaglandin D2, a bronchoconstrictor, is the principal cyclooxygenase metabolite of arachidonic acid that is released upon the activation of mast cells and is also synthesized by human alveolar macrophages. We performed bronchoalveolar lavage in five patients with chronic stable asthma, before and up to nine minutes after local provocative challenge with Dermatophagoides pteronyssinus. The lavage fluid was analyzed for products of arachidonic acid metabolism. Prostaglandin D2 levels in all five patients rose an average of 150-fold, from less than 8 to 332 +/- 114 pg per milliliter (mean +/- SEM; P less than 0.050), after local instillation of the antigen. Levels of 15-hydroxyeicosatetraenoic acid, which may also have a role in the pulmonary allergic response, were detectable in lavage fluid before challenge and increased after provocation with the antigen in four of the five patients. The activity of beta-glucuronidase, an enzyme released by macrophages and mast cells upon stimulation, tended to increase in the lavage fluid after provocation in all patients. These studies provide evidence that the release of prostaglandin D2 into the airways is an early event after the instillation of D. pteronyssinus in patients who are sensitive to this antigen.

Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response

“…However, depending on the stimulus and according to the PGE 2 receptors recruited, the effects of PGE 2 on the immunostimulatory functions of differentiated DC are diverse and sometimes opposite [31]. PGD 2 represents another major cyclooxygenase metabolite produced in vivo during inflammation, particularly during allergic reactions [32]. Along with its dual role in the genesis and in the control of inflammatory reactions, PGD 2 is thought to be an important component of the immune system.…”

“…Since micromolar concentrations of PGD 2 are detected in certain noninflamed tissues [42] such as the spleen and the bone marrow, it may be the case that PGD 2 modulates DC functions under steady-state conditions. Moreover, the enhanced production of PGD 2 in peripheral sites during inflammation, particularly during the allergic reaction [32] or tumor formation [43], highlights its role on DC functions in pathological conditions and suggests that PGD 2 may be an important component in the control of the immune response in these diseases.…”

BAY u3405 an antagonist of thromboxane A2‐ and prostaglandin D2‐induced bronchoconstriction in the guinea‐pig

“…Increased levels of metabolites of thromboxane A2 (TXA2) have been measured in the plasma and urine following antigen provocation in asthmatics (Green et al, 1974;Shepherd et al, 1985;Sladek et al, 1990) and increased prostaglandin D2 (PGD2) and TXA2 levels have been observed in bronchoalveolar lung fluid obtained following antigen challenge (Murray et al, 1986;Wenzel et al, 1989;Liu et al, 1990). …”

Essential role for hematopoietic prostaglandin D2 synthase in the control of delayed type hypersensitivity

“…Thereafter, 15-deoxy-⌬ 12,14 -PGJ 2 (15d-PGJ 2 ) and ⌬ 12 -PGJ 2 are generated from PGJ 2 by albuminindependent and -dependent reactions, respectively (7). PGD 2 is emerging as one of the predominant factors released in large amounts by mast cells during asthmatic attacks in humans (8). PGD 2 binds to and activates two G-protein-coupled receptors, DP1 and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th type 2 cells), also known as DP2.…”