<i>Background:</i> Patients with systemic mastocytosis have increased numbers of mast cells in the bone marrow and other organs, such as the liver, spleen, gastrointestinal tract and skin. Symptoms result from the local and remote effects of mediator release from mast cells and from the local effects of increased mast cell numbers in various organs. Patients with mast cell activation experience many of the same clinical symptoms as do patients with systemic mastocytosis from chronic or spontaneous release of mast cell mediators. We report 4 patients with mast cell activation symptoms from selective release of prostaglandin (PG) D<sub>2</sub>, but not histamine, and their improvement with aspirin therapy. <i>Methods:</i> Bone marrow biopsy specimens obtained from 4 patients with symptoms suggestive of mastocytosis were examined by tryptase immunostaining. Baseline levels of serum tryptase and urinary 11β-PGF<sub>2</sub><sub>α</sub> and N-methylhistamine were obtained. In 2 of the 4 patients, urinary 11β-PGF<sub>2</sub><sub>α</sub> and N-methylhistamine samples were also measured during acute symptoms. <i>Results:</i> Baseline increase in urinary excretion of the PGD<sub>2</sub> metabolite 11β-PGF<sub>2</sub><sub>α</sub> was found in 2 patients. In the remaining 2 patients, baseline levels of urinary 11β-PGF<sub>2</sub><sub>α</sub> and N-methylhistamine were normal, but during acute symptoms, the excretion of 11β-PGF<sub>2</sub><sub>α</sub> increased markedly. Treatment with aspirin resulted in normalization of 11β-PGF<sub>2</sub><sub>α</sub> excretion in the 2 patients with elevated baseline levels and in prevention of symptoms in all 4 patients. <i>Conclusions:</i> These results suggest that mast cell activation may be manifested by a selective excessive release of PGD<sub>2</sub>. These patients respond to administration of aspirin but not to antihistamines.
Abstract Eosinophil adhesion and degranulation appear to be associated with cell death. Eosinophils bound avidly and degranulated with secretory immunoglobulin A (slgA)- and IgG-coupled Sepharose 4B beads but bound poorly and did not degranulate with ovalbumin beads. Through the use of dye staining, we found that about 50% of the bound eosinophils were dead by 4 h, regardless of the protein coating. Colchicine and reduced calcium concentration inhibited binding to beads and eosinophil degranulation in a concentration-dependent manner but did not decrease the percentages of dead bound eosinophils. Electron microscopy showed that eosinophils bound to and spread over bead surfaces. Typical granule exocytosis with release of membrane-free granules occurred in about 20% of bound eosinophils. Eosinophil degeneration and lysis with release of membrane-coated granules occurred in about 50% of bound eosinophils; often only membrane-bound granules were present. Therefore, bound eosinophils degranulate both by classical exocytosis and by release after cytolytic degeneration. By increasing the numbers of bound cells, both IgG and sIgA increase the numbers of dying cells.
