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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Knowledge of the relative contributions of mast cells and neurons to the overall pool of histamine in the brain is a prerequisite to determining the significance and role of this amine in brain function. Consequently, we analyzed the levels of brain histamine in four genotypes (+/+, W/+, Wv/+, and W/Wv) of WBB6F1 mice, whose numbers of brain-associated mast cells vary in a genotypically specific manner. Although mast cell numbers ranged from a total absence of mast cells (W/Wv) to an average of about 500 mast cells/brain (W/+), no significant differences between genotypes were found in the quantities of histamine in whole brains, brain regions, or crude subcellular fractions. Thus, in this strain of mice, mast cells are not a significant source of histamine in the brain. This suggests that most of the histamine is of neuronal origin. Since neuronal histamine levels are maintained only by continued histidine decarboxylase activity, complete inhibition of this enzyme by alpha-fluoromethylhistidine, a "suicide" inhibitor of histidine decarboxylase, would totally deplete W/Wv mice of brain histamine. This was not found to occur in the W/Wv mice, suggesting that neuronal stores of histamine can be maintained in the absence of histidine decarboxylase, or that an additional nonneuronal, non-mast cell source of histamine exists in the W/Wv mouse brain.
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PMID:The significance of mast cells as a source of histamine in the mouse brain. 669

Diets containing egg white, casein, menhaden fish meal, soy protein or wheat gluten were fed to rats to assess the impact of dietary protein (and other nutrients) on gastric functions. The menhaden fish meal group exhibited increases in stomach histidine decarboxylase (HDC) activity, histamine concentration, as well as acid secretion when compared with the control, casein group. When rats were fed amino acid-supplemented casein or fish meal diets to simulate each other's amino acid profile, a small increase in gastric HDC activity, histamine content and acid secretion was observed in comparison with the unsupplemented casein or fish meal groups. The high mineral content of menhaden fish meal (15%) was thought to be a potential inducing factor for gastric histamine metabolism and acid secretion. Adding fish meal ash to the casein diet or to a cod fillet diet elevated stomach HDC activity and histamine concentration significantly. Furthermore, when calcium (Ca) was added to the casein diet to simulate its high content in menhaden fish meal (7.8%), similar elevated levels of gastric histamine were obtained for the Ca-supplemented casein group as for the fish meal group. The role of Ca could be due to release of gastrin, which results in release of stomach histamine, or by facilitating mast cell histidine incorporation with subsequent histamine synthesis.
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PMID:Gastric histamine metabolism and acid secretion in rats as influenced by diet and nutrient content. 682 9

Preincubation with (S)-alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, was found to markedly reduce, but not eliminate, the uptake of [3H]histidine by rat peritoneal mast cells. The Vmax for histidine transport for cells in which decarboxylation of histidine had been completely inhibited was 11.9 pmoles per min per 10(6) cells, compared to a Vmax of 18.9 pmoles per min per 10(6) cells in the presence of active mast cell histidine decarboxylase. The Km of uptake was 139 microM in the presence of alpha-fluoromethylhistidine, several times higher than the Km of 44.0 microM in the uninhibited cell. alpha-Fluoromethylhistidine did not inhibit mast cell uptake of phenylalanine, a competitive inhibitor of histidine uptake but not a substrate for histidine decarboxylase; nor did it inhibit the uptake of histidine by non-mast cells, which lack histidine decarboxylase. Levels of intracellular [3H]histidine in mast cells were similar in the presence and absence of the decarboxylase inhibitor. Based on these observations, we propose that intracellular decarboxylation of histidine in the mast cell serves to specifically enhance the uptake of histidine by the relatively non-specific amino acid transporter present in the plasma membrane of the cell.
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PMID:Histidine uptake by isolated rat peritoneal mast cells. Effect of inhibition of histidine decarboxylase by alpha-fluoromethylhistidine. 683 Jun 20

1 An attempt has been made to monitor simultaneously the changes in blood flow, histamine content, histidine decarboxylase (HDC) activity and mast cell population in rat skin isografts and allografts. 2 The histamine content in rat skin allografts during rejection was decreased in contrast with our earlier observation in rabbits. 3 Although no definite correlation has been found between blood flow changes, histamine content or HDC activity, a reciprocal relationship appeared to exist between histamine content and HDC activity in the skin grafts, which might be a reflection of the immunosuppressive activity of this amine. 4 The immunosuppressive agent, cyclosporin-A (20 mg/kg daily) was able to prolong skin allograft survival and prevent the changes in histamine and HDC activity in allografts. 5 Possible implications of these findings are discussed in relation to current knowledge concerning the interactions between endothelial cells, lymphocytes and mast cells/basophils in graft rejection.
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PMID:Blood flow, histamine content and histidine decarboxylase activity in rat skin grafts and their modification by cyclosporin-A. 704 88

The synthesis and degradation of histamine by dog fundic mucosa was studied by using cells dispersed by enzymatic digestion and separated sequentially by velocity sedimentation in an elutriator rotor, and by density gradient. Histidine decarboxylase activity was found in appreciable amounts in fractions highly enriched in mast cells when these cells were studied intact, whereas only trace activity was detected in homogenates of these mucosal mast cells or of whole mucosa. Unlike the rat gastric mucosal histamine cell, dihydroxyphenylalanine decarboxylase activity was not present in the canine fundic mast cell. Serotonin, which is found in the rat peritoneal mast cell, was not detectable in the canine mast cell. The histamine-degrading enzyme, histamine methyltransferase, was also present in gastric mucosal cells, but not diamine oxidase. This methyltransferase activity was primarily associated with parietal cells and was not found in the mast cell-enriched functions. For comparison, fractions containing 60%-80% mast cells were enriched by elutriation from enzyme-dispersed cells of canine liver. As with the gastric mast cells, histidine decarboxylase activity was found in intact cell, but it was lost upon cell disruption.
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PMID:Histamine synthesis by intact mast cells from canine fundic mucosa and liver. 705 26

Enriched preparations of intact histamine-containing cells were obtained from rat stomach by enzymatic digestion and density-gradient separation techniques. The distribution of histamine in the various density-gradient fractions was highly correlated with that for both histidine decarboxylase and DOPA-decarboxylase. The fractions with the highest content of these substances (density about 1.040) contained 8%-12% of cells which by electron microscopy had the characteristic appearance of an enterochromaffinlike cell. The distribution of these cells in the density gradient appeared to correlate with the distribution of histamine. The gastric histamine cells differed from the rat peritoneal mast cells in that they possessed neither serotonin nor receptors for IgE and did not release histamine upon exposure to compound 48/80. The rat peritoneal mast cell, on the other hand, had high histamine (17 pg/cell) and serotonin (0.6 pg/cell) contents but lesser amounts of soluble histidine decarboxylase and little DOPA-decarboxylase activity. These studies provide further evidence that in rat gastric mucosal histamine is stored in a cell having the morphologic and biochemical characteristics of an endocrinelike cell and the ability to take up and decarboxylate biogenic amines.
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PMID:Isolation of histamine-containing cells from rat gastric mucosa: biochemical and morphologic differences from mast cells. 720 43

The specific activation of mast cells in situ causes vigorous local mast-cell mediated angiogenesis (MCMA). The mast cell is a major source of histamine and, as recently reported, specific histamine H1- and H2-membrane receptor antagonists are able individually to significantly suppress MCMA in rats, as assessed using the mesenteric window angiogenesis assay (MWAA). In addition to membrane receptors for histamine, a type of intracellular histamine receptors, designated Hic, has been described. It is now demonstrated that the potent Hic-receptor antagonist DPPE (N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl), administered parenterally, stimulates MCMA significantly in rats, as quantified by the MWAA. Although the target cell(s) are not known, there are several ways by which their Hic receptors could be activated: uptake of histamine released from mast cells, mobilization from preformed cytoplasmic and nuclear stores, and production of de novo histamine by histidine decarboxylase activity. The fact that the occupancy by histamine of H1- and H2-membrane receptors stimulates MCMA and the occupancy by histamine of Hic inhibits MCMA suggests that endogenous histamine is capable of regulating angiogenesis by a dual mode of action. This is apparently the first report ascribing a dual role of this type in angiogenesis to a single molecule.
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PMID:Evidence of a dual role of endogenous histamine in angiogenesis. 754 Apr 12

The mast cell-deficient [Ws/Ws (White spotting in the skin)] rat was investigated with regard to the origin of histamine in the brain. No mast cells were detected in the pia mater and the perivascular region of the thalamus of Ws/Ws rats by Alcian Blue staining. The histamine contents and histidine decarboxylase (HDC) activities of various brain regions of Ws/Ws rats were similar to those of +/+ rats except the histamine contents of the cerebral cortex and cerebellum. As the cerebral cortex and cerebellum have meninges that are difficult to remove completely, the histamine contents of these two regions may be different between Ws/Ws and +/+ rats. We assume that the histamine content of whole brain with meninges in Ws/Ws rats is < 60% of that in +/+ rats. So we conclude that approximately half of the histamine content of rat brain is derived from mast cells. Next, the effects of (S) alpha-fluoromethylhistidine (FMH), a specific inhibitor of HDC, on the histamine contents and HDC activities of various regions of the brain were examined in Ws/Ws rats. In the whole brain of Ws/Ws rats, 51 and 37% of the histamine content of the control group remained 2 and 6 h, respectively, after FMH administration (100 mg/kg of body weight). Therefore, we suggest that there might be other histamine pools including histaminergic neurons in rat brain.
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PMID:Brain histaminergic system in mast cell-deficient (Ws/Ws) rats: histamine content, histidine decarboxylase activity, and effects of (S) alpha-fluoromethylhistidine. 754 15

1. Our previous work has shown that injection into mice of lipopolysaccharide (LPS) and the cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) induces histidine decarboxylase (HDC), the enzyme forming histamine, in various tissues such as liver, lung, spleen and bone marrow, but not in the blood. The induction of HDC also occurs in nude mice and mast cell-deficient mice. On the other hand, haematopoietic cytokines such as IL-3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) only induce HDC in the haematopoietic organs, i.e. bone marrow and spleen. In the present study, the effect of macrophage depletion on the induction of HDC was examined. 2. On day 1 after a single intravenous injection of a macrophage depletor (liposomes encapsulating dichloromethylene diphosphonate, which is toxic when ingested into macrophages), macrophages were almost completely depleted in the liver and reduced by about 50% in the spleen and bone marrow, but not significantly affected in the lung. On day 3, the degrees of the depletion were similar to those of day 1. In the spleen, macrophages were depleted in the red pulp, and there was a structural destruction. 3. In macrophage-depleted mice, the induction of HDC by LPS, IL-1 alpha or TNF-alpha was not impaired in the liver, and was potentiated in the lung and bone marrow. The induction of HDC was decreased only in the spleen at day 3. 4. HDC was not induced by LPS in the spleen of the adult rat, which is correspondingly inactive in haematopoiesis.5 These results indicate that the major cells in which HDC activity is induced in response to LPS, IL-1 and TNF are not circulating granulocytes, circulating monocytes, T cells derived from thymus, mast cells or phagocytic macrophages. Based on these results, we discuss the possibility that the major cells in which HDC was induced in non-haematopoietic and haematopoietic organs were endothelial cells and haematopoietic precursor cells respectively.
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PMID:Effects of macrophage depletion on the induction of histidine decarboxylase by lipopolysaccharide, interleukin 1 and tumour necrosis factor. 771 16

Murine interleukin-3 (IL-3) has extensive N-linked glycosylation. Experiments were performed to determine whether the T cell-derived glycosylated IL-3 differs in its biological activity in vivo when compared with a chemically synthesized form of nonglycosylated IL-3. Groups of mice were treated by intravenous injection with identical units of IL-3 bioactivity as determined in vitro in a cell-proliferation assay. Mice that were treated with seven 5000-unit doses of either form of IL-3, given in 12-hour intervals, showed a small but significant increase in the frequency of mast cell precursor cells in the spleen and of IL-3-responsive colony-forming unit cells (CFU-C). There was no difference in potency of glycosylated and nonglycosylated IL-3. Induction, by IL-3, of histidine decarboxylase in bone marrow and spleen cells was used as a second measure for IL-3 bioactivity. Both IL-3 preparations showed good in vivo histidine decarboxylase inducing activity; however, T cell-derived glycosylated IL-3 was significantly more effective than synthetic IL-3 in inducing the enzyme histidine decarboxylase in bone marrow and in spleen cells. Pharmacokinetic studies showed that chemically synthesized IL-3 was cleared about twice as fast as the T cell-derived IL-3 and that there may be some tissue trapping of glycosylated IL-3. The shorter in vivo half-life of nonglycosylated IL-3 appears to have significant pharmacological consequences on the short-term effect of inducing histidine decarboxylase activity, but not on the effect of the long-term treatment of IL-3 on stimulating the increase of hematopoietic progenitor cells.
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PMID:Carbohydrate does not modulate the in vivo effects of injected interleukin-3. 792 73


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