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

Endothelial surface expression of P-selectin and subsequent leukocyte rolling in venules can be induced by mast cell-derived histamine and binding of thrombin to protease-activated receptor-1 (PAR1). We hypothesized that activation of endothelial PAR2 by mast cell tryptase or other proteases also contributes to inflammatory responses. Leukocyte rolling flux and rolling velocity were assessed by intravital microscopy of the cremaster muscles of wild-type mice following perivenular micropipette injections of a control (LSIGRL) or PAR2-activating (SLIGRL) oligopeptide. Injection of SLIGRL increased mean rolling leukocyte flux fraction from 34 +/- 11 to 71 +/- 24% (p < 0.05) and decreased mean rolling velocity from 63 +/- 29 to 32 +/- 2 micrometer/s (p < 0.05). No significant changes occurred with control peptide injection. To further evaluate the role of PAR2 in inflammatory responses, PAR2-deficient mice were generated by gene targeting and homologous recombination. Perivenular injections of SLIGRL resulted in only a small increase in rolling leukocyte flux fraction (from 21 +/- 8 to 30 +/- 2%) and no change in rolling velocity. Leukocyte rolling after surgical trauma was assessed in 9 PAR2-deficient and 12 wild-type mice. Early (0-15 min) after surgical trauma, the mean leukocyte rolling flux fraction was lower (10 +/- 3 vs 30 +/- 6%, p < 0.05) and mean rolling velocity was higher (67 +/- 46 vs 52 +/- 36 micrometer/s, p < 0.01) in PAR2-deficient compared with control mice. The defect in leukocyte rolling in PAR2-deficient mice did not persist past 30 min following surgical trauma. These results indicate that activation of PAR2 produces microvascular inflammation by rapid induction of P-selectin-mediated leukocyte rolling. In the absence of PAR2, the onset of inflammation is delayed.
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PMID:Delayed onset of inflammation in protease-activated receptor-2-deficient mice. 1108 91

To study early events in mast cell / basophil development, the phenotype of a panel of murine cell lines at various stages of differentiation was determined. Based on the expression on various mast cell-specific proteases and several additional hematopoietic differentiation markers, the cell lines CFTL-15 and MCP5 / L were clearly identified as mast cells, although with a relatively immature phenotype. These two cell lines express the high-affinity IgE receptor alpha-chain, the mouse mast cell protease (MMCP)-5 and the carboxypeptidase A (CPA). Bone marrow-derived mast cells and the transplantable mast cell tumor MTC were shown to express the IgE receptor alpha-chain, MMCP-5 and CPA, as well as the mast cell tryptase MMCP-6 and the chymase MMCP-4, a protease expressed only during late stages of mast cell differentiation. These two cell types thus display a more mature mast cell phenotype. In contrast, the cell lines P815 and 32D cl3 did not express any mast cell differentiation markers. Interestingly, the IC-2 cell line was shown to express several markers for immature mast cells and in addition MMCP-8, a serine protease which may represent a marker for mouse basophils. By antibody staining, almost all IC-2 cells were shown to express MMCP-8. This indicates that individual cells may simultaneously express both mast cell and basophil markers. Moreover, these findings suggest that an early branch point in hematopoietic development where mast cells and basophils have a common precursor cell may exist.
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PMID:Murine mast cell lines as indicators of early events in mast cell and basophil development. 1109 57

HYPOTHESIS: Idiopathic and allergic rhinitics have similar mucosal mast cell and IgE+ cell distribution. INTRODUCTION: The pathophysiology of idiopathic rhinitis (IR) is unknown but patients differ from those with allergic rhinitis (AR) in that they do not express IgE. Our study is novel because we investigated: (1) three study groups chosen prospectively using strict selection criteria over a 4-year period; and (2) mast cell and IgE+ cell counts were on full-thickness, full-length inferior turbinate mucosa. METHODS: Patient groups: allergic (n = 17); idiopathic: (n = 16); and normal controls (n = 9). Immunohistochemistry: mast cell and IgE+ cell detection using anti-mast cell tryptase and anti-IgE antibodies with an avidin-biotin (peroxidase) complex on paraffin processed tissue. Morphometry: sections were divided into three strata comprising an epithelial layer and two submucosal layers. Statistics: Mann-Whitney non-parametric analysis. alpha = 0.05, beta = 0.2. RESULTS: The power of the study was 89%. Mast cells (P = 0.03) and IgE+ cells (P < 0.05) were significantly increased in the epithelium of idiopahtic and allergic rhinitis mucosa compared to the normal control. More IgE+ cells were counted in the AR and IR groups compared to the controls in all three strata. CONCLUSION: Mast cells and IgE+ cells are involved in the pahtophysiology of IR. We propose that IR may be a variant form of AR involving a localized IgE-mediated inflammatory response.
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PMID:Idiopathic and allergic rhinitis show a similar inflammatory response 1112 70

Synaptotagmin I (STG I) is a Ca(2+) sensor and one of the synaptic vesicle proteins that mediate exocytosis. To determine the mechanism of release of large granules from mast cells, we studied by immunohistochemistry the presence of STG I in mast cells in normal human tissues simultaneously with the mast cell markers mast cell tryptase (tryptase) and c-kit. The tumor cells of systemic mast cell disease (SMCD) and a human mast cell leukemia cell line (HMC-1) were also examined. Human mast cells in normal tissues and the tumor cells of SMCD expressed STG I as well as mast cell tryptase (tryptase) and c-kit. STG I mRNA and its products in HMC-1 were examined by RT-PCR analysis and immunocytochemistry, respectively. STG I expression in HMC-1 cells was compared with that in cells stimulated and non-stimulated by phorbol 12-myristate 13-acetate and also with that in NB-1 and PC12 cells, known to express STG I. STG I mRNA was detected in both non-stimulated and stimulated HMC-1 cells and in NB-1 and PC12 cells. STG I immunoreactivity was weaker than NB-1 or PC12 immunoreactivity. However, it increased in the stimulated HMC-1 cells. Mast cells expressed STG I in various states. STG I may mediate exocytosis of large granules in mast cells.
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PMID:Synaptotagmin I expression in mast cells of normal human tissues, systemic mast cell disease, and a human mast cell leukemia cell line. 1118 37

Mast cell involvement in chronic gastritis in children was analyzed. 25 children with normal mucosa (controls), 20 children with chronic gastritis and 28 children with chronic gastritis and infected Helicobacter pylori were included to the study. Bioptic material from antrum and corpus of the stomach were stained with toluidine blue and anti-human mast cell tryptase to evaluate mast cell density. Changes in mast cells number were also estimated in 7 children before and after successful eradication of Helicobacter pylori infection. Mast cell density was significantly greater in children with chronic gastritis with or without Helicobacter pylori infection when compared to the controls. Mast cell degranulation was demonstrated by electron microscopy in children with chronic gastritis and infected Helicobacter pylori. Mast cell through it's numerous mediators may play a key role in chronic gastritis especially when Helicobacter pylori infection is present.
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PMID:[Mast cells in chronic gastritis of children]. 1139 16

We determined the distribution of mast cells in nasal mucosa and studied their proliferation. Inferior turbinate mucosa was sampled in 13 patients with allergic rhinitis (allergic group) and 5 without (non allergic group) and stained immunohistochemically using anti mast cell tryptase antibody, anti-c-kit antibody, anti-PCNA antibody, and anti mast cell chymase antibody. Tissue sections stained with anti tryptase antibody revealed a higher degree of infiltration of tryptase-positive cells, i.e., mast cells, in the allergic group than in non allergic group. In the allergic group, the number of tryptase-positive cells, c-kit-positive cells, and PCNA-positive cells was significantly greater in the epithelium and shallow lamina propria than that in the deep lamina propria. Tryptase-positive, c-kit-positive cells, i.e., c-kit-positive mast cells, and tryptase-positive, PCNA-positive cells, i.e., PCNA-positive mast cells, were also abundunt in the epithelium and shallow lamina propria. The stem cell factor and c-kit receptor are reported to play a primary role in mast cell differentiation and proliferation. PCNA-positive cells represent actively proliferating cells. Based on the above, we concluded that mast cells in the epithelium and shallow lamina propria in the allergic group differentiated and proliferated more actively than those in the deep lamina propria.
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PMID:[Differentiation and proliferation of mast cells in nasal mucosa]. 1143 40

Renal interstitial fibrosis is characterized by increased proliferation of fibroblasts and excessive accumulation of extracellular matrix. Mast cell tryptase has been implicated in the development of tissue fibrosis in skin and lungs. However, the significance of mast cell tryptase in human renal diseases has not been investigated. The potential role of mast cell-derived tryptase in the development of renal fibrosis was studied using immunohistochemical techniques and cultured human renal fibroblast cell lines. Semiquantitative immunostaining analysis of samples from 70 patients with several renal diseases, including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic tubulointerstitial nephritis (n = 18), revealed that the degree of renal interstitial fibrosis was well correlated with the number of infiltrating tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in damaged glomeruli in any form of renal disease. [(3)H]Thymidine uptake experiments demonstrated that DNA synthesis by cultured renal fibroblasts was increased with the concentration of tryptase (0.5 to 5 nM) coincubated with heparin and was suppressed by coincubation with the protease inhibitors leupeptin and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by fibroblasts but exhibited less effectiveness, compared with the combination of tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by fibroblasts. Metabolic [(35)S]methionine-labeling experiments with cultured renal fibroblasts indicated that tryptase increased the synthesis of fibronectin and collagen type I, in a dose-dependent manner. These findings suggest that mast cell tryptase plays a role in the proliferation and extracellular matrix protein production of renal interstitial fibroblasts and thus contributes to the development of renal interstitial fibrosis.
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PMID:Role of mast cell tryptase in renal interstitial fibrosis. 1146 39

Mast cells are likely to play a role in angiogenesis under pathological conditions. Solid tumor growth is dependent on angiogenesis, but the influence of mast cells on angiogenesis in non-Hodgkin's lymphoma, (NHL) is not clear. We investigated mast cell number and vessel count in 61 cases of NHL. We also evaluated expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), both important cytokines for angiogenesis. The number of mast cells was greater in T-cell lymphomas than in B-cell lymphomas. Of the T-cell lymphomas, the greatest number of mast cells was observed in the angioimmunoblastic T-cell lymphoma (AIL). In all NHLs, significant correlation was found between vessel count and the number of mast cells (p < 0.0001) and between vessel count and the number of VEGF-expressing cells (p < 0.05) but not between vessel count and bFGF-expressing cells. Strong correlation was detected between the number of mast cells and the number of VEGF-expressing cells (p < 0.0001) in all NHLs. Double fluorescence staining of VEGF mRNA and mast cell tryptase revealed that mast cells expressed VEGF mRNA. Our data suggest that mast cells play a very important role in angiogenesis by expressing VEGF in NHL, especially in AIL.
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PMID:Angiogenesis and mast cells in non-Hodgkin's lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma. 1169 1

Mast cell proteinases are important inflammatory mediators in man and other species, but until now there has been no investigation of the nature of equine mast cell proteinases. These studies describe the purification and characterisation of two proteolytic components from equine mastocytoma tissue, detected using chromogenic substrates for trypsin and chymotrypsin. Following chromatographic purification, the trypsin-like component was found to be equine mast cell tryptase by N-terminal amino acid sequencing, showing a close similarity with human tryptase-beta (85% identity over 20 residues). It also had similar subunit molecular size (34-36kDa by SDS-PAGE) and substantially similar cleavage specificity to human tryptase-beta with the substrates tested. A 32kDa chymotrypsin-like component was also purified from mastocytoma extract, and termed equine mast cell proteinase-1 (eqMCP-1). The N-terminal amino acid sequence of eqMCP-1 was very similar to human granzyme H (95% over 19 residues). Rabbit antisera directed against tryptase and eqMCP-1 both detected equine mast cells by immunohistochemistry, and will be of use in future clinical studies of the relevance of mast cell proteinases in equine allergic disease.
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PMID:Characterisation of tryptase and a granzyme H-like chymase isolated from equine mastocytoma tissue. 1173 Sep 33

We reported previously that mast cell tryptase is a growth factor for dog tracheal smooth muscle cells. The goals of our current experiments were to determine if tryptase also is mitogenic in cultured human airway smooth muscle cells, to compare its strength as a growth factor with that of other mitogenic serine proteases, and to determine whether its proteolytic actions are required for mitogenesis. Highly purified preparations of human lung beta-tryptase (1-30 nM) caused dose-dependent increases in DNA synthesis in human airway smooth muscle cells. Maximum tryptase-induced increases in DNA synthesis far exceeded those occurring in response to coagulation cascade proteases, such as thrombin, factor Xa, or factor XII, or to other mast cell proteases, such as chymase or mastin. Irreversibly abolishing tryptase's catalytic activity did not alter its effects on increases in DNA synthesis. We conclude that beta-tryptase is a potent mitogenic serine protease in cultured human airway smooth muscle cells. However, its growth stimulatory effects in these cells occur predominantly via nonproteolytic actions.
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PMID:Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions. 1179 23


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