Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MAST CELLS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed1994

Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase-related serine protease.

In previous work the primary structure of a previously unknown protease was deduced from the sequence of a dog mastocytoma cDNA. The predicted preproprotein shares some features with mast cell tryptases but is no more than 49% identical in sequence to known trypsin-like enzymes, including dog tryptase. This study explores the expression of this protein, termed dog mast cell protease-3 (dMCP-3). A polyclonal Ab was raised to a peptide corresponding to residues 166-181 of the deduced sequence. Anti-dMCP-3(166-181) Ig recognizes dMCP-3 expressed as a CheY fusion protein in Escherichia coli and binds to a approximately 36-kDa protein in extracts of dog mastocytomas. The Ab does not recognize dog tryptase, dMCP-3s closest known relative in mastocytoma cells. When used with fluorescein-conjugated and alkaline phosphatase-conjugated secondary Abs, anti-dMCP-3(166-181) Ig yields punctate cytoplasmic staining in mastocytoma cells, suggesting localization to intracellular granules. Staining is greatly reduced by preincubation with synthetic dMCP-3 peptide, supporting the specificity of the Ab. Immunohistochemical staining of normal dog tissues reveals scattered dMCP-3 reactive cells in skin, intestine, trachea, and lung parenchyma. Double staining with Ab and methylene blue shows that anti-dMCP-3(166-188) Ig recognizes extravascular mononuclear tissue cells with metachromatic granules. In addition, cytoplasmic staining is seen in polymorphonuclear leukocytes within vessels in tissue sections and in leukocytes harvested from blood. Hybridization of dMCP-3 cDNA to dog skin RNA provides further evidence of dMCP-3 gene transcription in normal tissue. Thus, this study provides immunochemical evidence of dMCP-3 expression in dog mast cell tumors, normal tissue mast cells, and neutrophils.

Amino Acid Sequence↗
PubMed2001

Angiogenesis and mast cells in non-Hodgkin's lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma.

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.

Cell Count↗
PubMed2004

TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells.

Recent studies have revealed that murine bone marrow-derived cultured mast cells (BMMC), which are phenotypically immature mast cells, express functional TLR2 and TLR4 that recognize distinct pathogen-associated molecules. However, it remains relatively uncertain whether mast cells express other TLR. We recently established a method to obtain large numbers of murine fetal skin-derived cultured mast cells (FSMC); these cells exhibit important features of connective tissue type mast cells. Working with FSMC and BMMC, the TLR mRNA expression profiles were compared between both cell types. Although TLR2 and TLR4 mRNA were detected in both cells at comparable levels, TLR3, TLR7, and TLR9 mRNA were expressed by FSMC at higher levels than by BMMC, suggesting distinct TLR expression profiles among different mast cell populations. With respect to their functional aspects, FSMC, but not BMMC, dose dependently produced proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (RANTES, MIP-1alpha, and MIP-2) in response to poly(I:C), R-848, and CpG oligodeoxynucleotide, which are TLR3, TLR7, and TLR9 activators, respectively. Interestingly, these TLR activators failed to induce degranulation and IL-13 production by both mast cells, although peptidoglycan and LPS (TLR2 and TLR4 activators, respectively) induced IL-13 production by both cells. Mast cells, thus, may have potential to recruit other immune cells to the infected sites by responding to various bacterial and viral components through TLR signaling pathways, presumably being involved in initiating innate immunity and subsequently linking innate and acquired immune responses.

Animals↗
PubMed1998

Demonstration of mast-cell chemotactic activity in nasal lavage fluid: characterization of one chemotaxin as c-kit ligand, stem cell factor.

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean=125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis.

Allergens↗
PubMed1991

Evidence for in vivo degradation of C3a anaphylatoxin by mast cell chymase. I. Nonspecific activation of rat peritoneal mast cells by C3ades Arg.

The anaphylatoxin C3a (125I-HC3a) is extensively degraded when exposed to isolated rat mast cells (RMC). Degradation occurs without prior stimulation of these cells. The protease responsible for C3a degradation has been identified as chymase. Mixed peritoneal cells, containing equal numbers of mast cells compared with incubates containing more highly purified RMC, promoted less degradation of the C3a molecule than did the purified RMC. These variable levels of spontaneous activation (ie, chymase release) of RMC in vitro were concluded to be a function of the cellular handling and isolation procedures. No degradation occurred when low levels of 125I-HC3ades Arg (10(-8) mol/l [molar]) were introduced in the peritoneum of a rat, unless the mast cells were stimulated by prior introduction of specific activators. Evidence that the enzyme being released in the peritoneal cavity of rats was chymase was provided both by its appearance after adding specific mast cell activators (ie, compound 48/80 and anti-IgE [gamma E immunoglobulin]) and by inhibition with chymostatin. Because 125I-HC3ades Arg at low levels (10(-8) mol/l) was not degraded in the rat peritoneum, expression of chymase by the rat mast cells could be monitored in situ during mast cell stimulation. 125I-HC3ades Arg was rapidly converted (in 2 to 5 minutes) to smaller fragments in the peritoneal cavity of the rat after either 10 micrograms of compound 48/80 or anti-IgE was injected. Introduction of higher levels of HC3a or HC3ades Arg (2.5 to 5.0 x 10(-6) mol/l) to the peritoneal cavity of the rat stimulated both chymase release and HC3a degradation without other mast cell activators being present. HC3ades Arg was equally as effective in vivo as HC3a in stimulating the rat peritoneal mast cell to release chymase. It was concluded that the mechanism of RMC activation by C3a (C3ades Arg) was nonspecific and similar to the process by which polyamines and polycations stimulate mast cells, as C3a is a highly cationic molecule. The fact that C3a may in turn be destroyed in minutes by the recruited protease (chymase) defines a potentially important physiologic control mechanism. This cellular control process, demonstrated here for rat mast cells, may function in other animals, including man, for regulating tissue levels of factors such as the anaphylatoxins that are potentially capable of mast cell activation through nonspecific (polycationic) mechanisms.

Animals↗
PubMed1987

Regulation of the delayed hypersensitivity reaction in the lung reflected as mononuclear, mast cell and mucus cell appearance after T helper cell depletion and adoptive transfer.

Epicutaneous sensitization with picrylchloride (PiCl) induced a strongly delayed hypersensitivity (DH) reaction in mice. Local challenge in the airways of these mice resulted in increased numbers of mononuclear cells, mast cells and mucus cells. Depletion of T helper cells in vivo by treatment with monoclonal antibody (GK 1.5) inhibited the DH reaction. This treatment also resulted in a decrease in the number of mononuclear and mucus cells in the lung after intranasal challenge. The DH reaction was transferred to recipients with immune lymph node cells and spleen cells from mice sensitized epicutaneously with PiCl. The recipient mice also showed a slight increase in the number of mononuclear cells in the lung after intranasal challenge. These results indicate that T cells are not only involved in the DH reaction but also in the accompanying lung reaction.

Animals↗
PubMed1995

Angiogenic factors stimulate mast-cell migration.

Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell-shaped dose-response curve. Another potent angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase-inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.

Animals↗
PubMed2000

Murine mast cell lines as indicators of early events in mast cell and basophil development.

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.

Animals↗
PubMed2005

Human mast cells release Interleukin-8 and induce neutrophil chemotaxis on contact with activated T cells.

BACKGROUND: Mast cells have recently been shown to control neutrophil recruitment during T-cell mediated cutaneous DTH reaction in vivo through TNF-alpha and MIP-2, the functional murine analogue of human IL-8. Although the nature of signals transmitted from T cells which activate mast cells has not yet been defined, we hypothesized that a direct cross-talk (i.e. heterotypic adhesion) between these two cell populations exists, as has previously been reported. AIMS: The present study was aimed at gaining insight into the functional role of mast cell-T cell contact in expression and release of IL-8, and its effect on neutrophil chemotaxis. METHODS: The IL-8 gene expression was identified by Affymetrix GeneChip arrays, validated by RT-PCR and the protein measured by ELISA. Chemotaxis was evaluated by using a modified Boyden chamber assay. RESULTS: Mast cells were found to express and release significantly higher concentrations of IL-8 on incubation with membranes obtained from activated, as compared to resting T cells. Supernatants obtained from these activated mast cells induced significant neutrophil chemotaxis that was inhibited by neutralizing mAb to IL-8. CONCLUSIONS: Thus, activated T cells, on heterotypic adhesion to mast cells, deliver the necessary signals for the latter to release cytokines and chemokines necessary for cell migration to sites of antigen challenge, thereby facilitating T-cell mediated inflammatory processes.

Autocrine Communication↗
PubMed2000

Chondroitin sulphate inhibits connective tissue mast cells.

1. Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly inflammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-inflammatory molecules that include histamine, cytokines and proteolytic enzymes. 2. Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory effect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell 'stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed off, while the effect of cromolyn was limited by rapid tachyphylaxis. 3. Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo- and monosaccharides were not as effective as the polysaccharides. 4. Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes. 5. Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications.

Animals↗
PubMed1992

Synthetic substrates and inhibitors for serine proteases from lymphocytes, mast cells, semen, and blood.

The substrate specificity of several serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, seminal fluid, and blood plasma has been determined with synthetic peptide thiobenzyl ester and p-nitroanilide substrates. Several new enzymatic activities have been discovered. A variety of inhibitors such as isocoumarins, trifluoromethyl ketones, and peptide chloromethyl ketones were used to study these enzymes and were found to be potent inhibitors.

Amino Acid Sequence↗
PubMed2005

Restoration of hepatic mast cells and expression of a different mast cell protease phenotype in regenerating rat liver after 70%-hepatectomy.

Mast cells (MC) can undergo significant changes in number and phenotype; these alterations result in the differential expression of growth factors and cytokines. Kit ligand (KL; stem cell factor) is produced by mesenchymal cells, and in the liver by biliary epithelial cells. Recent studies suggest that KL, and its receptor c-kit, may be involved in liver regeneration after loss of liver mass. However, KL is also the major growth, differentiating, chemotactic, and activating factor for MC. The aim of our study was to elucidate the dynamics and phenotype of hepatic MC and KL/c-kit expression during liver regeneration after partial (70%) hepatectomy in the rat. Regenerating livers were harvested after 1, 3, 7, and 14 days, respectively (n = 6 each day). MC were stained for naphthol-AS/D-chloroacetate esterase and counted as MC per bile ductule. MC phenotype was assessed by rat MC protease (RMCP)-1 and -2 immunofluorescence staining, in order to distinguish RMCP-1 positive connective tissue MC (CTMC) from RMCP-2 positive mucosa MC (MMC). mRNA expression of RMCP, c-kit, and the differentially spliced variants of KL was quantified by RT-PCR. MC counts per bile ductule decreased in regenerating rat liver tissue at day 3, compared with native livers, and became normal thereafter. Hepatic MC were predominantly of a CTMC phenotype expressing RMCP-1, as previously published; after hepatectomy, between 76 and 99% of all MC double-expressed RMCP-1 and -2, compatible with an MMC phenotype. The ratio of the two alternatively spliced mRNAs for KL (KL-1 : KL-2), and c-kit mRNA expression did not differ significantly between regenerating livers and the livers of sham operated animals. These results suggest that hepatic mast cells are restored during liver regeneration after partial hepatectomy in the rat. Restored MC express an MMC phenotype, suggesting migration from outside into the regenerating liver. Alternative splicing of KL is affected by the surgical procedure in general, and, together with its receptor c-kit, doesn't seem to be involved in liver regeneration after partial hepatectomy in the rat. Further functional studies, and studies in regenerating human livers might offer the possibility of elucidating the role of the hepatic mast cell, and its different protease phenotypes during liver regeneration after surgical loss of liver mass.

Animals↗
PubMed1989

[Basal cell carcinoma and mast cells].

The histology of 17 cases of basal cell carcinoma and dermis next to the carcinoma was observed. The results showed that the mast cell number was markedly increased in the dermis near the basal cell carcinoma. There was an increase in the collagen fibers between the carcinoma and dermis tissues, forming a thin membrane around the carcinoma tissue. These findings suggest that the carcinoma-associated antigen may activate the lymphocytes to produce certain lymphokine which stimulates the proliferation and differentiation of the mast cell precursors. Histamine and other active mediators released from mast cells stimulate fibroblasts to synthesize collagen fibers which form a thin membrane between the carcinoma and dermis. The membrane plays a protective role against tumor dissemination.

Biopsy↗
PubMed1993

Reversible expression of mouse mast cell protease 2 mRNA and protein in cultured mast cells exposed to IL-10.

BALB/cJ mouse mast cells derived by culturing bone marrow progenitor cells in WEHI-3 cell-conditioned medium (BMMCW) do not contain mouse mast cell protease 2 (mMCP-2) mRNA, but these cells can be induced to express this transcript after exposure to rIL-10. To study the translation and granule accumulation of mMCP-2 in rIL-10-treated BMMC (BMMCW+IL-10), a rabbit antibody was developed to a synthetic peptide that corresponds to the novel amino acid sequence in mMCP-2 at residues 56 to 71. After affinity purification, this antibody, anti-mMCP-2(56-71) IgG, reacted in SDS-PAGE/immunoblots against a 28-kDa protein in BMMCW+IL-10 that had the N-terminal amino acid sequence of mMCP-2. As assessed immunohistochemically, mMCP-2 protein accumulated in the secretory granules of Kirsten sarcoma virus-immortalized mouse mast cells, BMMCW+IL-10, and the mucosal mast cells present in the jejunum of Trichinella spiralis-infected BALB/cJ mice. Time course analyses of the induction of mMCP-2 mRNA and protein in BMMCW+IL-10 revealed that these cells contain a high steady-state level of mMCP-2 mRNA 24 h after their exposure to rIL-10. Although a small amount of immunodetectable mMCP-2 protein is present in the cells treated for 24 h, large amounts of this protease are not obtained until 7 days of treatment of the cells with rIL-10. Time course analyses of the loss of mMCP-2 mRNA and protein in BMMCW+IL-10 revealed that the steady-state level of mMCP-2 mRNA decreased dramatically 24 h after rIL-10 was removed from the culture medium, but that the level of mMCP-2 protein did not decline measurably until day 5 of culture. The fact that the steady-state levels of mMCP-2 mRNA and protein in BMMC can both be reversibly altered by culturing these mast cells in the presence and absence of rIL-10 suggests that the phenotype of mast cells is not fixed. Rather, it is in a dynamic state regulated by the cytokine network to which mast cells are exposed in their different microenvironments.

Amino Acid Sequence↗
PubMed1987

The regulation of inflammatory mediator production by mast cell products.

Mast cells are prominent in the airways and have been implicated in the pathophysiology of asthma. The ability of mast cells to generate or release the vasoactive/spasmogenic mediators histamine, adenosine, PGD2, sulfidopeptide leukotrienes, and platelet-activating factor is thought relevant to immediate bronchospastic responses in association with mucus secretion and airway edema. Mast cell elaboration of chemotactic factors and release of enzymes with both tryptic and chymotryptic specificity is held responsible for later reactions in which airway inflammation is prominent and nonspecific bronchial hyperreactivity is present. Recent evidence indicates that in addition to direct effect of these mast cell products some mast cell mediators themselves modulate inflammatory mediator production. Thus, adenosine, by interacting with A2 receptors on the surface of mast cells, markedly augments mast cell release of preformed granule associated mediators. Mast cell-derived chemotactic factors, exemplified by low molecular weight eosinophil directed molecules, can induce cell specific synthesis of inflammatory lipids such as platelet-activating factor. These findings only begin to suggest the richness of possibilities for mast cell regulation of the inflammatory response and underline the reality that the inflammatory response in lung as in all tissue is extremely complex and dependent upon cell-to-cell communication for its full expression.

Animals↗
PubMed2001

Mast cells can revert dexamethasone-mediated down-regulation of stem cell factor.

Mast cell hyperplasia can be causally related with chronic inflammation and liver fibrosis. Their survival and proliferation is dependent upon locally produced growth factors, the major one being the stem cell factor (SCF). Glucocorticoids can decrease mastocytosis, down-regulating the mast cell production of pro-inflammatory factors or inhibiting the expression of SCF in stroma. We compared dexamethasone effect on SCF expression in co-cultures of mast cells with NIH/3T3 fibroblasts or with primary cultures of activated hepatic stellate cells. Dexamethasone abrogated the NIH/3T3 stroma capacity to sustain mast cell proliferation, but not of hepatic stellate cells, at the post-transcriptional level. Mast cells reverted completely dexamethasone effect on hepatic stellate cells, increasing their SCF synthesis and transport. In both models, dexamethasone inhibited the mast cell spreading on the stroma, which was thus not required for mast cell survival and proliferation. Liver pathologies associated with mast cell hyperplasia are not expected to be sensitive to glucocorticoid treatments.

3T3 Cells↗