Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When peritoneal resident cells (PRCs) of genetically mast cell-deficient WBB6F1-W/Wv mice were cultured in vitro for 5 h at 37 degrees C, their histidine decarboxylase [HDC, L-histidine carboxylase, E.C. 4.1.1.22] activity increased 10-fold. Since inhibitors for energy production and mRNA and protein syntheses inhibited this increase of HDC activity, it appeared to represent de novo synthesis of the enzyme, i.e., induction. This increase was followed by an increase in the amount of histamine in the culture medium of the cells, indicating that histamine synthesized by the induced HDC was not stored in the cells but was quickly released. Mast cells were not involved in the HDC induction, because the extents of HDC induction in PRCs of W/Wv and wild type +/+ mice were similar. The removal of T cells with anti-Thy-1,2 antibody and complement from the PRCs did not affect the HDC induction, but the removal of phagocytes decreased the induction to one-tenth in spite of a 2-fold increase in the proportion of B cells in the PRCs. After separation of the PRCs into adherent and non-adherent fractions, the increase in HDC activity was found to be associated with the adherent fraction that was mostly positive to esterase staining. These results suggest that HDC was induced in peritoneal macrophages.
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PMID:In vitro increase of histidine decarboxylase activity and release of histamine by peritoneal resident cells of mast cell-deficient W/Wv mice; possible involvement of macrophages. 245 55

Chemokines probably mediate inflammation in asthma by acting on endothelial cells, alveolar cells, neutrophils, eosinophils, basophils, mast cells, monocytes, and lymphocytes, which are inhibited by corticosteroids. In 1995, we found that MCP-1 provokes mast cell aggregation and [3H]5HT-release in cultured mast cells. In another study, MCP-1 and RANTES revealed to have a potent chemoattractive effect on basophilic cells originating from the rat skin. In this inflammatory model, RANTES also attracted eosinophils and macrophages along with basophilic cells. The effect of RANTES on inducing HDC mRNA was dose dependent. MCP-1 and RANTES provoked histamine release in intradermal mast cells and prostaglandin D2 generation. These effects clearly show that RANTES and MCP-1 are mediators of acute inflammatory responses. In chronic inflammatory reactions, MCP-1 is also present as we show in a study recently published by our group. In this paper, we found that MCP-1, strongly mediates the recruitment of mononuclear cells in the granuloma formed by KMnO4. In addition, MCP-1 mediated a parasitic infection caused by Trichinella spiralis in mice. Our data strongly demonstrate that chemokines, such as RANTES and MCP-1, mediate acute inflammatory response.
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PMID:Chemokines in inflammatory states. 1047 17

Mast cells are differentiated in vitro from bone marrow precursors. In this study the development of bone marrow-derived mast cells was examined from histidine decarboxylase deficient (HDC-/-) and wild-type mice in the presence of IL-3. The number of non-adherent, tryptase- and c-kit-positive mast cells in bone marrow-derived cultures of HDC(-/-) mice was decreased compared to that of wild-type (HDC+/+) animals, but within the tryptase- and c-kit-positive cells there was no difference in the expression intensity of both markers between the two groups. Furthermore, less serine proteases mMCP5, mMCP6 and FcepsilonRIalpha mRNA were detected in bone marrow-derived cell cultures originating from HDC-/- mice. Antigen-provoked degranulation through high-affinity FcepsilonI receptor was also lower in HDC-/- mice. The colony assays in semisolid medium yielded a significantly lower ratio of mixed colonies and higher proportion of macrophage colonies from HDC-/- mice-derived bone marrow compared to the wild-type. In the course of the differentiation of HDC-/- --derived mast cells exogenously added histamine is unable to substitute the endogenously missing histamine. Concordantly, alpha-fluoromethyl-histamine, the specific inhibitor of HDC, revealed only a marginal inhibition on the differentiation of tryptase-positive mast cells from wild-type mice. These findings suggest that the effect of histamine on the IL-3-dependent development of bone marrow-derived mast cell differentiation during the early period is crucial and irreplaceable.
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PMID:Bone marrow-derived mast cell differentiation is strongly reduced in histidine decarboxylase knockout, histamine-free mice. 1193 74

We have analyzed the role of histamine in the angiogenesis of the granulation tissue in histidine decarboxylase-deficient (HDC(-/-)) mice, mast cell-deficient mice (WBB6F1-W/W(V)), and their corresponding wild-type mice (HDC(+/+) and WBB6F(1)(+/+)). In HDC(+/+) mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of anti-vascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC(-/-) mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC(+/+) mice. The topical injection of histamine or the H(2) agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC(-/-) mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/W(V) and WBB6F1(+/+) mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.
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PMID:Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. 1195 88

The role of brain histamine on seizure development of pentylenetetrazol (PTZ)-induced kindling was examined in H(1)-receptor gene knockout (H(1)KO), histidine decarboxylase-deficient (HDC(-/-)) and mast cell-deficient (W/W(v)) mice. All H(1)KO, HDC(-/-) and W/W(v) mice had accelerated seizure development of PTZ-induced kindling when compared to their respective wild-type mice. The daily PTZ-kindling increased histamine content in the cortex and diencephalon of H(1)KO mice, whereas the histamine content in the diencephalon of W/W(v) mice was decreased. The present study indicates that histamine plays a suppressive role in seizure development through H(1)-receptors.
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PMID:Chemical kindling induced by pentylenetetrazol in histamine H(1) receptor gene knockout mice (H(1)KO), histidine decarboxylase-deficient mice (HDC(-/-)) and mast cell-deficient W/W(v) mice. 1264 74

Targeted disruption of the histidine decarboxylase gene (HDC(-/-)), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC(-/-) mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC(-/-) mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1alpha-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-kappaB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC(-/-) mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption.
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PMID:Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss. 1271 72

In an air pouch-type carrageenin-induced inflammation model in rats, the selective cyclooxygenase (COX)-2 inhibitor NS-398 dose dependently inhibited the granulation tissue formation, angiogenesis and the level of vascular endothelial growth factor (VEGF) in the granulation tissue. In culture of the minced granulation tissue, PGE2 induced VEGF production in a concentration-dependent manner. Histamine also induced VEGF production in the granulation tissue in vitro. The H2 receptor antagonist cimetidine, the cAMP antagonist Rp-cAMP and the protein kinase A inhibitor H-89 suppressed the histamine-induced VEGF production in the granulation tissue. However, the H1 receptor antagonist pyrilamine maleate, the H3 receptor antagonist thioperamide, the protein kinase C inhibitors Ro 31-8425 and calphostin C or the tyrosine kinase inhibitor genistein showed no effect. Subcutaneous implantation of a cotton thread in the dorsum of histidine decarboxylase-deficient (HDC-/-) mice, but not in mast cell-deficient (WBB6F1-W/Wv) mice, induced less angiogenesis with lower levels of VEGF in the granulation tissue than in their corresponding wild-type (HDC+/+ and WBB6F1(-)+/+) mice. In HDC-/- mice, the topical injection of histamine or the H2 receptor agonist dimaprit rescued the defective angiogenesis and granulation tissue formation. In addition, cimetidine but not pyrilamine maleate and thioperamide inhibited the histamine-induced angiogenesis in the granulation tissue in HDC-/- mice. These findings suggest that PGE2 and histamine augment angiogenesis in the inflammatory granulation tissue by inducing VEGF production, and histamine induces VEGF production possibly through the H2 receptor--cAMP--protein kinase A pathway.
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PMID:Regulation by prostaglandin E2 and histamine of angiogenesis in inflammatory granulation tissue. 1277 86

Histamine plays an important role in the regulation of gastric acid secretion; however, its role in maintenance of gastric morphology remains unclear. To clarify the necessity of histamine for gastric mucosal development and maintenance, we evaluated two different kinds of mice that lacked either mast cells (one of the gastric histamine-producing cell types) or histidine decarboxylase (HDC; a histamine-synthesizing enzyme). Measurements of stomach weight, intragastric pH, mucosal histamine levels, as well as serum gastrin and albumin levels were performed in mice. Gastric mucosal appearance was examined by immunohistochemical techniques. Although gastric mucosal histamine levels in mast cell-deficient mice were half of those observed in the wild-type mice, intragastric pH, serum gastrin levels, and gastric morphology at 12 mo were unchanged compared with the wild-type mice. In contrast, HDC-deficient mice possessed no detectable gastric histamine, but did exhibit hypergastrinemia, as well as marked increases in intragastric pH and stomach weight compared with the wild-type mice. Histological analysis revealed that 9-mo-old HDC-deficient mice demonstrated hyperplasia in the oxyntic glandular base region, as well as increased numbers of parietal and enterochromaffin-like cells. These results indicate that enterochromaffin-like cell-derived histamine is potentially involved in gastric mucosal morphology regulation.
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PMID:Lack of histamine alters gastric mucosal morphology: comparison of histidine decarboxylase-deficient and mast cell-deficient mice. 1527 53

Tryptase and chymase are the two major granular proteases present in human mast cell (MC)s. We used oligonucleotide microarray to measure the levels of approximately 22,000 transcripts in cord blood-derived MCs at 4 weeks, 8 weeks, 12 weeks and 18 weeks in culture. Tryptase (TPSB2) was expressed at the highest level among all transcripts and its expression level reached a plateau at 8 weeks. On the other hand, the expression level of chymase (CMAI) doubled every 4-6 weeks. A similar tendency was found at the protein levels with FACS analysis. After filtering the transcripts with MC-specificity, hierarchical clustering analysis identified 494 and 81 transcripts in the same clusters with tryptase and chymase, respectively. MC-specific genes, KIT and HDC were found in the tryptase cluster. In the chymase cluster, a critical suppressor for cell senescence, BMI1 and the several related genes were found, suggesting that chymase expression may be closely related to cell senescence/quiescence events.
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PMID:Identification of tryptase- and chymase-related gene clusters in human mast cells using microarrays. 1643 34

Mast cells synthesize and store histamine, a key immunomodulatory mediator. Polyamines are essential for every living cell. Previously, we detected an antagonistic relationship between the metabolisms of these amines in established mast cell and basophilic cell lines. Here, we used the IL-3-driven mouse bone marrow-derived mast cell (BMMC) culture system to further investigate this antagonism in a mast cell model of deeper physiological significance. Polyamines and histamine levels followed opposite profiles along the bone marrow cell cultures leading to BMMCs. alpha-Difluoromethylornithine (DFMO)-induced polyamine depletion resulted in an upregulation of histidine decarboxylase (HDC, the histamine-synthesizing enzyme) expression and activity, accompanied by increased histamine levels, specifically during early stages of these cell cultures, where an active histamine synthesis process occurs. In contrast, DFMO did not induce any effect in either HDC activity or histamine levels of differentiated BMMCs or C57.1 mast cells, that exhibit a nearly inactive histamine synthesis rate. Sequence-specific DNA methylation analysis revealed that the DFMO-induced HDC mRNA upregulation observed in early bone marrow cell cultures is not attributable to a demethylation of the gene promoter caused by the pharmacological polyamine depletion. Taken together, the results support an inverse relationship between histamine and polyamine metabolisms during the bone marrow cell cultures leading to BMMCs and, moreover, suggest that the regulation of the histamine synthesis occurring during the early stages of these cultures depends on the concentrations of polyamines.
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PMID:Polyamines affect histamine synthesis during early stages of IL-3-induced bone marrow cell differentiation. 1956 74


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