Uptake and metabolism of histamine by neoplastic mast cells (original) (raw)
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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.
Frontiers in Oncology
Cancer microenvironment is complex and consists of various immune cells. There is evidence for mast cell (MC) infiltration of tumors, but their role thereof is poorly understood. In this study, we explored the effects of mast cell and their mediators on the growth of hematological cancer cells. The affect is demonstrated using RBL-2H3 MCs, and YAC-1, EL4 and L1210 as hematological cancer cell lines. Direct contact with MCs or stimulation by their mediators caused growth inhibition of YAC-1 cells, growth enhancement of EL4 cells and no change in growth of L1210 cells. This effect was confirmed by cancer cell recovery, cell viability, mitochondrial health, and cell cycle analysis. MCs showed mediator release in direct contact with tumor cells. MC mediators' treatment to YAC-1 and EL4 yielded exactly opposite modulations of survival markers, Survivin and COX-2 and apoptosis markers, Caspase-3, Bcl-2, in the two cell lines. Histamine being an important MC mediator, effect of histamine on cell recovery, survival markers and expression of various histamine receptors and their modulation in cancer cells was studied. Again, YAC-1 and EL4 cells showed contrary histamine receptor expression modulation in response to MC mediators. Histamine receptor antagonist co-treatment with MC mediators to the cancer cells suggested a major involvement of H2 and H4 receptor in growth inhibition in YAC-1 cells, and contribution of H1, H2, and H4 receptors in cell growth enhancement in EL4 cells. L1210 showed changes in the histamine receptors' expression but no effect on treatment with receptor antagonists. It can be concluded that anti-cancerous action of MCs or their mediators may include direct growth inhibition, but their role may differ depending on the tumor.
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.
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.
Journal of Veterinary Internal Medicine, 2003
Plasma histamine concentrations (PHCs) were measured serially over 9 months or until death in 11 dogs with mast cell tumors (MCTs). Eight dogs had grossly visible disease and the other 3 dogs had microscopic disease. Initial PHCs in the dogs with gross disease were significantly higher than PHCs in healthy dogs (median, 0.73 ng/mL and 0.19 ng/mL respectively; P & lt;009), whereas initial PHCs in dogs with microscopic disease showed no difference from controls. Seven dogs subsequently had progressive increases in PHC, and developed hyperhistaminemia (median, 14.0 ng/mL; range, 5.11–30.1 ng/mL). These 7 dogs died from MCTs, and 1 had general weakness with rapid lysis of a large tumor burden after radiation therapy. PHCs of the other 4 dogs were less than 1 ng/mL during the study. These 4 dogs were still alive with adequate control of the tumor at the conclusion of the study. Four of the 11 dogs initially had gastrointestinal (GI) signs, which abated soon after administration of histam...
Experimental & Molecular Medicine, 2007
The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H 1 and H 2 and that the selective H 1 antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H2 antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of β-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and β-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/ antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth.
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.