Bone marrow-derived mast cell differentiation is strongly reduced in histidine decarboxylase knockout, histamine-free mice (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.
International Immunopharmacology, 2004
Histamine modulates immune responses. There are at least two ways histamine might be supplied: one is its release from cells that pool pre-formed histamine and the other is its de novo formation via induction of histidine decarboxylase (HDC). Lipopolysaccharide (LPS) and the proinflammatory cytokine interleukin (IL)-1 induce a marked elevation of HDC activity in various tissues or organs. To examine the contribution of mast cells to HDC induction in mice given LPS or IL-1, we examined the effects of LPS and IL-1 on HDC activity and/or histamine content in various organs (liver, lung, spleen or bone marrow) in mast cell-deficient mice (W/W v), their normal littermates (+/+) and BALB/c mice deficient in IL-1a, IL-1h and tumor necrosis factor (TNF)-a (IL-1ah/TNFaKO mice). In non-stimulated mice, the histamine in the lung and spleen was contained largely within mast cells. The LPS-stimulated increase in HDC activity in a given organ was similar between +/+ and W/W v mice, and between IL-1ah/TNFaKO BALB/c and control BALB/c mice, and led to increases in histamine. In W/W v and +/+ mice, IL-1a also elevated HDC activity. These results suggest that (i) in liver, lung and spleen, either the major cells supplying histamine via HDC induction in response to LPS and IL-1 are not mast cells, or mast cells are not a prerequisite for the induction of HDC; (ii) the cells in which HDC is induced by LPS and IL-1 are similar or identical in a given organ; and (iii) neither IL-1 nor TNF-a is a prerequisite for the induction of HDC by LPS.
European Journal of Immunology, 2006
Histamine is released in inflammatory reactions and exerts an immunoregulatory function on cells present in the microenvironment. In this study, we compared the effect of histamine on degranulation of mast cells derived from animals bearing a parasitic infection with those from uninfected animals. Peritoneal mast cells (PMC) were obtained 24 days after infection of Wistar rats with Toxocara canis. The degree of degranulation was assessed either morphologically or by measuring the release of b-hexosaminidase and TNF-a. Non-purified PMC or mast cells immunomagnetically purified with mAb AA4 were used. An increase in degranulation of non-purified mast cells from infected animals was observed after incubation with histamine in vitro or when histamine was injected into the peritoneal cavity. When a purified mast cell population was used, this effect was no longer observed. Supernatants from spleen cells stimulated with histamine induced degranulation of purified mast cells, and again, this was potentiated with PMC from infected animals. However, when supernatants from peritoneal macrophages similarly stimulated were used, a reduction in the degranulation of PMC from infected animals was observed. Our results suggest that histamine may act as a regulator of mast cell degranulation, thus modulating inflammatory responses due to infection with certain parasites.
Mice lacking histidine decarboxylase exhibit abnormal mast cells
FEBS Letters, 2001
Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histaminesynthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDCdeficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes. ß
Cellular Immunology, 1990
There is growing interest in studying pathways of mast cell activation. In a mouse model of chronic graft-vs-host disease (cGVHD) extensive mast cell activation and degranulation occurs in vivo coincident with the development of dermal fibrosis. An interesting feature of this model is that the mast cell reaction is slow to develop, occurring over a period of weeks and waning by 300 days. The aim of our work was to investigate the effects of supernatants from splenocytes of such cGVHD mice (cGVHD sups) on mouse and rat peritoneal mast cells cocultured with 3T3 skin fibroblasts. We found that cGVHD sups are able to release histamine from both mouse and rat cultured mast cells in a slow fashion. Histamine release became evident only after 5-8 days of coculture of the mast cells with the cGVHD supernatants and thereafter decreased to basal levels. Mast cell activation due to cGVHD supernatants was a noncytotoxic event as demonstrated by mast cell counts in the cocultures and by the ability of mast cells to exclude trypan blue. Mast cells that had been activated by incubation with the cGVHD sups were as responsive to stimulation with either anti-IgE antibodies or compound 48/80 as were mast cells incubated with control sups. Supernatants from mice early in GVHD (Days 11-28) were most active in promoting histamine release. Supernatants from spleens of mice which had GVHD for 290 days and where the mast cells had returned to full granulation in vivo were inactive. This is the first in vitro study demonstrating slow mast cell histamine release instituted by other cells, namely the splenocytes of cGVHD mice.
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 in vitro differentiation of mast cells
The Journal of Cell Biology
When cells from lymph nodes or thoracic duct of mice hyperimmunized with protein antigens are cultivated on embryo monolayers in the presence of the antigen, numerous clones of mast cells appear. The histochemical and ultrastructural characteristics of the cells permit their identification as mast cells and distinguish them from the phagocytic histiocytes that usually arise in abundance in similar cultures from unimmunized mouse cells or from immunized mouse cells cultured in the absence of the antigen. Only a few colonies of mast cells appeared in the latter cultures. The basis for the induction of mast cell differentiation is not known.
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.
Development of human mast cells in vitro
Proceedings of the National Academy of Sciences, 1989
Nucleated cells of human umbilical cord blood were cocultured with mouse skin-derived 3T3 fibroblasts. After 7-8 weeks in culture, when the number of the other hematopoietic cells declined, metachromatic granule-containing mononuclear cells appeared in the cultures, and the number of the cells increased up to 12 weeks. After 11-14 weeks in culture, the metachromatic mononuclear cells comprised a substantial portion of the cultured cells. These cells contained 1.8-2 micrograms of histamine per 10(6) cells and bore receptors for IgE. All of the cells contained tryptase in their granules. Electron microscopic analysis showed that these cells were mature human mast cells, clearly different from the basophilic granulocytes or eosinophils that arise in a variety of circumstances in cord blood cell cultures. Most of the cultured mast cells expressed some granules with regular crystalline arrays and contained both tryptase and chymase, and thus resembled human skin mast cells.