thromboxane-b2 and Mastocytosis

Mastocytosis is a disorder of mast cell proliferation that occurs in both cutaneous and systemic forms. The most frequent site is the skin.. The mast cell subtype of two patients with mastocytosis was investigated.. Immunohistochemical studies were performed on the skin or gastric mucosa or both of the two patients. Blood and urine levels of various mediators were measured for one patient.. Mast cells containing tryptase and chymase were the only type seen in the skin lesions of an 11-month-old boy with urticaria pigmentosa. Mast cells containing tryptase were predominant in lesions of the skin and gastric mucosa of a 41-year-old man with indolent systemic mastocytosis. However, mast cells containing tryptase and chymase were predominant in the nonlesional and the normal skin of this patient. Tryptase-positive cells were more numerous in lesional skin than nonlesional skin and normal skin. Elevated blood and urine levels of various mediators were decreased by means of combination therapy with ketotifen and ranitidine.. In indolent systemic mastocytosis, mast cell dynamics involve only cells containing tryptase. Release of mediators from mast cells may be inhibited by means of combination therapy with histamine H1 and H2 receptor antagonists.

Topics: Adult; Biopsy; Chymases; Dinoprostone; Histamine; Humans; Infant; Ketotifen; Leukotrienes; Male; Mast Cells; Mastocytosis; Ranitidine; Serine Endopeptidases; Thromboxane B2; Tryptases; Urticaria Pigmentosa

The clinical features of systemic mastocytosis have been ascribed to mast cell-dependent mediators, but there have been no studies of their release from isolated cells. We have investigated the release of histamine and eicosanoids from isolated spleen cells obtained from tissue of a mastocytosis patient undergoing therapeutic splenectomy. Dispersed cell preparations contained lymphocytes 65.9%, monocytes/macrophages 22.3%, neutrophils 9.9%, mast cells 1.1%, and eosinophils 0.8%; upon challenge with 0.1-3.0 microM A23187 they released histamine much greater than PGD2 greater than TXB2 greater than LTB4 greater than LTC4 approximately equal to LTD4 greater than LTE4. With immunological activation of passively sensitized cells, histamine and PGD2 release had similar dose-response characteristics, but TXB2, LTC4, LTD4, and LTE4 release differed in reaching maximum at 50 micrograms/ml and declining at 125 micrograms/ml anti-human IgE. Percoll centrifugation separated most of the histamine-containing cells to the middle of the gradient, but they were refractory to release with 0.3 microM A23187 or 50 micrograms/ml anti-IgE. Spontaneous release of histamine from these cells was not abnormally high (1.3%-4.5%). Electron microscopy of tissue sections revealed large numbers of mast cells with empty granules. It is possible that the refractory cells observed are such mast cells where intracellular histamine is no longer granule-associated. Most net histamine and PGD2 release was confined to cells at the bottom of the gradients (1.078-1.09 g/ml), although some release of PGD2 occurred near the top (1.05-1.058 g/ml). There was a significant correlation between the net release of histamine and PGD2 with both immunological (r = 0.92; n = 16) and A23187 (r = 0.97, n = 14) activation. These studies provide evidence for a link between PGD2 and histamine release in mastocytosis spleen cells.

Topics: Adult; Calcimycin; Calcium; Cell Fractionation; Histamine Release; Humans; Immunoglobulin E; Leukotriene B4; Male; Mastocytosis; Prostaglandin D2; Prostaglandins D; Spleen; SRS-A; Thromboxane B2