PGE suppresses excessive anti-IgE induced cysteinyl leucotrienes production in mast cells of patients with aspirin exacerbated respiratory disease.

BACKGROUND

Aspirin causes bronchospasm in patients with aspirin exacerbated respiratory disease (AERD). The contribution of mast cells to the increased cysteinyl-leucotrienes (cys-LTs) detected in AERD patients is however not defined.

AIMS OF THE STUDY

Effects of prostaglandin (PG) E(2) and inhibitors of cyclooxygenase (COX) and lipoxygenase (LO) pathways on mediator release from cultured mast cells of normal subjects, aspirin tolerant asthma (ATA) and AERD patients were compared to better define the role of mast cells in AERD.

METHODS

Mast cells were cultured from peripheral blood progenitors and were activated by anti-IgE. Histamine, PGD(2) and cys-LTs released were then determined.

RESULTS

Basal release of all three mediators was similar in all subjects. Although the release of all three mediators was increased by anti-IgE, mast cells from AERD patients produced significantly more cys-LTs (6.9 +/- 2.0 ng/10(6) cells) than normal and ATA subjects (2.3 +/- 0.8 and 1.7 +/- 0.5 ng/10(6) cells, respectively). While COX and LO pathway inhibitors did not affect anti-IgE induced histamine release, they significantly suppressed the production of PGD(2) and cys-LTs, respectively, in all patients. PGE(2) significantly enhanced anti-IgE induced histamine and PGD(2) release from mast cells of normal subjects but not those of ATA and AERD patients. In contrast, PGE(2) suppressed only anti-IgE induced cys-LTs release from mast cells of AERD patients.

CONCLUSION

We speculate that overproduction of cys-LTs is unique to mast cells of AERD patients and is particularly sensitive to suppression by PGE(2). Consequently reduction of PGE(2) production by aspirin removes this endogenous control of cys-LTs overproduction, resulting in asthma attack.