Effects of dimethylsulfoxide (DMSO), nocodazole, and taxol on mast cell histamine secretion (original) (raw)
Related papers
Mast Cell Degranulation and Histamine Release Observed in a New in Vitro System
Journal of Experimental Medicine, 1960
Mast cells participate in some types of inflammatory reactions involving changes in the microcirculation of certain tissues. Among the known vasoactive substances of importance, histamine has been found in mast cells (1) of several species of animals and in certain species serotonin is also present (2). A variety of substances (the formaldehyde polymer of p-methoxyphenethylmethylamine (48/80), ovomucoid, and dextran) when administered to the rat elicit an inflammatory response, cause histamine and serotonin release and the morphological change of degranulation . No clear description of the process involved in release of the active amines and other mast cell constituents has yet been presented. A major obstacle has been the lack of an appropriate way of observing the action of various agents on the structure of the mast cell and its constituents under controlled conditions. Hence, a new method of observation was sought to study the mechanism of mast cell secretion in vitro.
The mechanism of histamine release from mast cells
Biochemical Pharmacology, 1972
Mast cell secretion was studied in vitro using rat peritoneal cells stimulated by polymyxin B sulfate. The dose-response curve for histamine release was only slightly lowered when mast cells isolated by sedimentation through albumin solution (specific gravity, 1.100) were compared to cells not subjected to the isolation procedure. The release of N-acetyl+-glucosaminidase, a readily soluble component of mast cell granules, closely paralleled the release of histamine. However, little release occurred of two insoluble granule components, mast cell chymase and heparin, and their release was not dose dependent. These results indicated that histamine release from mast cells can occur in the absence of extrusion of their granules. Quantitative studies of the uptake of ruthenium red and morphologic studies of the distribution of ruthenium red and ferritin demonstrated that the granules are effectively extruded into an extracellular space tnat is confined to the cellular domain by a labyrinth of cytoplasmic processes. The secretory process of mast cells then appears to be effected through a sequence of membrane fusions that produce deep channels of extracellular space penetrating through the cell and enveloping the granules rather than by the propulsion of the granules to the cell surface with extrusion at that site.
Evidence of mast-cell histamine being mitogenic in intact tissue
Agents and Actions, 1985
In cultured rat mesentery there was a spontaneous release of about 45% of the histamine in 2 days, and a spontaneous marked increase in basal proliferation of the mesentery. The MC secretagogues, compound 48/80 and polymyxin B, released additional histamine and stimulated mitogenesis further. In contrast, 48/80 added to cultures of guinea-pig mesentery, the MC of which are unresponsive to the drug, did not affect the basal proliferation. However, exogenous histamine at 10 10 Mmitogenlcally stimulated the cultured guinea-pig mesentery. A histamine H2-reeeptor antagonist, which itself was mitogenieaUy inert, significantly suppressed the 48/80-1nduced MC-mediated mitogenesis in rat mesentery in vDo and in vitro. On the other hand, a histamine Hi-receptor antagonist did not affect this MCmediated mitogenesis in rat.
Cancer Chemotherapy and Pharmacology, 1992
We studied the histamine-releasing activity of several antineoplastic drugs on rat pleural and peritoneal mast cells. The drugs tested included the nitrogen mustards cyclophosphamide and ifosfamide, the nitrosourea carmustine, the triazene dacarbazine, the folic acid analogue methotrexate, the pyrimidine analogue cytarabine and fluorouracil, the vinca alkaloids vinblastine, vincristine and Vinoretbine, the epipodophyllotoxins etoposide and teniposide, and the enzyme L-asparaginase. Methotrexate, carmustine, fluorouracil, vinblastine and vincristine failed to elicit histamine release on rat mast cells. All of the other drugs evoked histamine release in both the presence and the absence of extracellular calcium, but ifosfamide, cytarabine and asparaginase induced a much lower release in the absence of this cation. The response elicited by cytarabine and etoposide was much higher in pleural than in peritoneal mast cells. These results indicate that some antineoplastic drugs may directly activate the release of histamine, which could contribute to some of their secondary effects.
Journal of immunology, 1982
Functional mast cells have been isolated from the lamina propria of the small intestine of rats infected with the nematode Nippostrongylus brasiliensis. The cells released histamine on challenge with specific antigen, anti-rat IgE, concanavalin A, and calcium ionophores but were less responsive than peritoneal mast cells (MMC) from the same animals. Intestinal mucosa mast cells (PMC) were refractory to the action of the basic secretagogues peptide 401 from bee venom and compound 48/80. The anti-allergic compounds disodium cromoglycate (less than or equal to 10(-3) M), AH 9679 (less than or equal to 10(-4) M), and theophylline (less than or equal to 10(-2)) did not inhibit antigen-induced histamine secretion by MMC, although these compounds were effective against PMC. In contrast, doxantrazole (10(-5) to 10(-3) M) inhibited the secretion of histamine from both MMC and PMC in a comparable dose-dependent fashion. Thus, we have established that mast cells from different sites are functi...
Dependence of histamine release from rat mast cells on adenosine triphosphate
Naunyn-Schmiedeberg's Archives of Pharmacology, 1972
Using pure populations of rat mast cells, the relation of the ATP content of the cells to histamine release induced by compound 48/80 has been studied. Variable ATP levels in the mast cells have been produced by incubation with appropriate concentrations of oligomycin. The dose-response curves of oligomycin for the inhibition of histamine release and for the reduction in the ATP content of the mast cells are similar. The concentration required for 500/0 inhibition of histamine release is, however, higher than that for 50o/0 reduction of the ATP level. Comparative study of the reduction of the ATP content and the inhibition of histamine release in samples of the same suspension of mast cells shows a linear relation between 10 to 90 ~ inhibition of histamine release and 40 to 95 ~ inhibition of ATP synthesis. The observations support the hypothesis that ATP is involved in the process of histamine release from mast cells induced by compound 48/80.
Local Mitogenic Effect of Tissue Mast Cell Secretion
Cell Proliferation, 1980
The effect of drug-induced mast cell secretion on proliferation .was studied in fibroblast-like and mesothelial-like cells in organ-cultured rat mesentery. Mast cell degranulation achieved by Compound 48/80 was followed by a marked mitogenic reaction in the surrounding tissue cells. The drug itself lacked mitogenic effect on cultured guinea-pig mesentery, the mast cells of which are unresponsive to the drug, and on a human normal fibroblast-like cell line. In contrast, histamine at about lo-'' M, a major mast cell component, induced marked mitogenesis in guinea-pig mesentery without causing degranulation of mast cells.
Histamine content and mast cell numbers in tissues of normal and athymic rats
Agents and Actions, 1986
Tissue histamine levels and mast cell numbers were determined in the skin, tongue and jejunum of female rnu/nu and rnn/+ rats aged between 5 and 29 weeks. The tongue and jejunal mucosa of rnn/nu rats had a larger mast cell density and histamine content than rnu/+. There was a marked increase in subepithelial mast cells in the skin of rnu/nu rats compared with their normal littermates, while mast cell numbers in the deep skin layer and the histamine content were similar in the two groups of rat. Subepithelial skin mast cells were smaller, of more variable shape and contained fewer granules than mast cells in the deep dermal layer, and, unlike the latter, did not emi t a yellow fluorescence after treatment with o-phthalaldehyde. The results indicate that the bulk of the skin histamine is contained in mast cells residing in deep skin layers. They also support the view that the thymus may have a suppressive effect on both mucosai and connective tissue mast cells in vivo.