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

Mast cells are critical effectors in many IgE-dependent responses, and the numbers and phenotype of certain mast cell populations can be influenced, through IL-3 and IL-4, by the same T cells that regulate IgE production. However, IgE can interact with cells other than mast cells, and different mast cell populations express significant variation in multiple important aspects of their phenotype, including mediator content and responses to cytokines and stimuli of activation. As a result it may be difficult to define the unique contributions of mast cells to IgE-dependent reactions. One approach for analysing the roles of various mast cell populations in individual biological responses is to attempt to elicit these reactions in mice in which the presence or absence of specific mast cell populations can be regulated experimentally. We have used genetically mast cell-deficient and mast cell-reconstituted mice to demonstrate that mast cells provide essential effector function in certain IgE-dependent responses involving the skin, stomach or lungs but are not necessary for the pulmonary alterations and death associated with active anaphylaxis. Similar approaches can be used to investigate the biological significance of the production, by mast cells stimulated with IgE and specific antigen, of cytokines similar or identical to IL-1, IL-3, IL-4, IL-5, IL-6, TNF-alpha/cachectin, IFN-gamma, GM-CSF, JE, MIP-1 alpha, MIP-1 beta and TCA3.
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PMID:Mast cells: immunologically specific effectors and potential sources of multiple cytokines during IgE-dependent responses. 251 50

The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells can be seen, e.g., in the intraepithelial cell layer after a provoked allergic reaction. Such accumulation probably requires directed migration of mature mast cells or their precursors. To study the migration of human mast cells we used as a model the human mast cell line, HMC-1, and stem cell factor-dependent (also referred to as mast cell growth factor or Kit ligand) cord blood-derived mast cells. The results show that stem cell factor is a potent chemotactic factor for human mast cells in vitro. The chemotactic response to SCF was found to be dose dependent, reaching a maximum at 50 ng/ml. The activity of SCF could be blocked by anti-SCF Abs. We also tested the effect of different intercrines, i.e., IL-8, MIP-1 alpha, MIP-1 beta, RANTES, and MCAF (also referred to as monocyte chemotactic protein 1), on human mast cell migration. Only RANTES was chemotactic for in vitro-developed mast cells. None of the tested intercrines induced migration of HMC-1 cells. For migration, the mast cells were dependent on binding to an extracellular matrix protein. Thus, coating of the filters with fibronectin was required, whereas collagen or laminin did not promote migration. Adhesion of HMC-1 cells to fibronectin could also be shown in an adhesion assay. In addition, expression of receptors for fibronectin could be detected on the surface of the mast cells. These results show that SCF is not only a growth and differentiation factor for human mast cells in vitro but also a potent chemoattractant for such cells.
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PMID:Stem cell factor is a chemotactic factor for human mast cells. 752 4

Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 micrograms/ml: 26.9 +/- 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 microgram/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3), or tonsils (n = 3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
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PMID:Differential response of human basophils and mast cells to recombinant chemokines. 754 Dec 56

We have previously reported that monocyte chemoattractant protein-1 (MCP-1) is the most potent histamine-releasing factor (HRF) for basophils. Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has modest histamine-releasing activity. The objective of this study was to investigate whether MCP-1 and MIP-1 alpha would activate mast cells in vivo and induce a cutaneous inflammatory reaction in mice. To this goal, mouse hind footpads were separately injected with 20 microliters of human recombinant MCP-1 or MIP-1 alpha (10(-7) M). Diluent was used as a control in the second footpad. The footpad-swelling response was measured at 30 min, 1 h, and then hourly for 6 h. Both MCP-1 (2.72 +/- 0.2 vs 2.1 +/- 0.03 mm for diluent, n = 8, p < 0.02) and MIP-1 alpha (3.0 +/- 0.1 vs 2.1 +/- 0.03 mm for diluent, n = 8, p < 0.02) induced an immediate swelling reaction. The immediate reaction was followed by a sustained late reaction that peaked within 1 h and lasted for more than 6 h. Histologic examination of the footpads, obtained at hour 2, revealed that MCP-1 caused mild mononuclear cell infiltrates, moderate degranulation of mast cells, and soft tissue swelling. In contrast, MIP-1 alpha induced a severe inflammatory reaction that consisted of neutrophils, mononuclear cells, and degranulated mast cells. Electron microscope examination of the tissue revealed features of extensive mast cell degranulation by MIP-1 alpha and to a lesser extent by MCP-1. Thus, we conclude that mast cells are activated on injection of MCP-1, whereas degranulation of mast cells and recruitment of leukocytes contribute to the footpad reaction induced with MIP-1 alpha.
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PMID:Macrophage inflammatory protein-1 alpha and monocyte chemoattractant peptide-1 elicit immediate and late cutaneous reactions and activate murine mast cells in vivo. 830 Nov 33

The proteolytic cleavage product of complement component 3, (C3a), is like C4a and C5a, is a potent anaphylatoxin and induces the production of inflammatory mediators in phagocytes. Notably, mast cells respond to C3a with the release of vasoactive substances, including histamine. We have examined the function and receptor binding of C3a in a human leukemic mast cell line, HMC-1. Similar to chemoattractant agonists in leukocytes, C3a induced rapid cytosolic free calcium concentration increases in HMC-1 cells. EGTA did not diminish this response, indicating that mobilizable Ca2+ was from intracellular stores. Receptors of C3a in HMC-1 cells couple in part to Bordetella pertussis toxin-sensitive G-proteins and, therefore, appear to belong to the family of serpentine receptors that require G-proteins for signal transduction. HMC-1 cells express two types of C3a receptors, C3aR1 and C3aR2, that were shown to bind 125I-C3a with high-(Kd1 = 2.1-4.8 nM) or low-affinity (Kd2 = 30-150 nM), and both receptors are expressed at high level: 3 x 10(5)-6 x 10(5) C3aR1/cell and 5 x 10(5)-2.3 x 10(6) C3aR2/cell. Results from cross-linking experiments with 125I-C3a fully agree with the presence of two different classes of C3a receptors in HMC-1 cells. Two membrane proteins with apparent molecular masses of 54-61 kDa (p57) and 86-107 kDa (p97) could be covalently modified with 125I-C3a, and this cross-linking was inhibited with an excess of unlabeled C3a. Many of the known agonists for leukocytes including 13 chemokines (IL-8, NAP-2, GRO alpha, ENA-78, IP10, PF4, MCP-1, 2 and 3, RANTES, MIP-1 alpha, MIP-1 beta and I309), three neuropeptides (neuropeptide Y, somatostatin and calcitonin), as well as C5a, did not activate HMC-1 cells, indicating that C3a is one of a few protein ligands for which this cell line expresses specific receptors. The apparent selectivity for C3a and the abundant expression of C3a receptors make the HMC-1 cell line an excellent choice for the cloning of the receptor genes.
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PMID:Expression of high- and low-affinity receptors for C3a on the human mast cell line, HMC-1. 862 64

Cell priming and stimulation of different cytokines (which include chemokines and growth factors) are typical features of human basophils. Recently, it has been shown that the macrophage chemotactic protein-1 (MCP-1), RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are potent direct secretagogues for human basophils and that interleukin-3 (IL-3), IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are priming factors for subsequent potentiation of mediator release from basophils induced by different stimuli. This observation may be clinically important for the activation and recruitment of inflammatory cells in different immune responses of the skin (e.g. late-phase reactions). The aim of the present study was to investigate whether cytokines and chemokines are also capable of priming or stimulating isolated human skin mast cells (SMC). SMC were either stimulated directly with the cytokines alone or preincubated with these factors for 10 min before being activated with suboptimal concentrations of anti-IgE, A23187 or substance P. IL-3, IL-5, GM-CSF, platelet factor-4 (PF-4), IL-8, MCP-1 and MIP-1 alpha (each at concentrations of 1 ng/ml to 1 microgram/ml, log steps) did not significantly modulate histamine release from SMC induced by the three different secretagogues. RANTES exhibited a weak but significant potentiating effect on IgE-mediated activation. Stem cell factor (SCF) as a positive control was able to prime mast cell histamine release strongly. In addition, PF-4, MCP-1, RANTES and MIP-1 alpha were incapable of inducing direct histamine release from SMC. In experiments with isolated human peripheral basophils, however, we observed potent Fc epsilon RI-mediated priming effects evoked through IL-3, IL-5 and GM-CSF. We conclude that SMC derived from healthy donors are not targets of (immuno)modulatory factors that prime or stimulate basophils.
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PMID:Effects of basophil-priming and stimulating cytokines on histamine release from isolated human skin mast cells. 884 26

Neutrophil (PMN) migration into the peritoneal cavity in response to fecal peritonitis is an important mechanism of host defense against bacterial invasion. We show that the murine C-X-C (PMN-specific) chemokine, macrophage inflammatory protein-2 (MIP-2), on intraperitoneal injection in mice, causes PMN migration into the peritoneum. MIP-2 mRNA and protein were expressed by peritoneal leukocytes after cecal ligation and puncture (CLP) in mice and neutralization of MIP-2 reduced peritoneal PMN migration. A prerequisite for neutrophil-endothelial adhesion and subsequent migration from the circulation is selectin-mediated rolling. Pretreatment of mice with an anti-P-selectin antibody before intraperitoneal injection of MIP-2 significantly reduced peritoneal PMN migration. However, there are no reports that a C-X-C chemokine can up-regulate endothelial selectins. We postulated that MIP-2, when injected intraperitoneally, interacts with a cell that is known to release factors that up-regulate endothelial selectins. A likely candidate is the mast cell, which contains histamine and tumor necrosis factor alpha (TNF-alpha), and both of these factors induce selectins. Intraperitoneally injected MIP-2 caused an early significant increase in peritoneal TNF-alpha, whereas histamine levels were unaffected. In a subsequent experiment, mast cell-deficient mice and their normal controls were then injected intraperitoneally with MIP-2 or underwent CLP. Significantly fewer PMNs migrated into the peritoneal cavity in the mast cell-deficient mice after MIP-2 injection or CLP. Thus, our findings indicate that mast cells and MIP-2 are necessary for PMN migration into the peritoneum in response to intra-abdominal infection, and that MIP-2 appears to facilitate this through an increase in TNF-alpha release.
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PMID:Regulation of early peritoneal neutrophil migration by macrophage inflammatory protein-2 and mast cells in experimental peritonitis. 1008 8

Mast cells (MCs) are known as key cells of immediate type hypersensitivity reactions. It has recently been shown that MCs regulate fibroblast proliferation by heterotypic cell-cell contact and secretion of interleukin-4 (IL-4) in vitro. It was therefore hypothesized that MCs may contribute to wound repair in vivo. Using immunohistology and in situ hybridization, the time course of mast cell recruitment and the expression of MC-attractant chemokines were analysed in a human skin wound-healing model, and the production of IL-4 by MCs in vivo was investigated. The data obtained indicate that the five-fold increase of the tryptase+ MCs at the fibrotic border of the wound within the first 10 days is the result of increased recruitment/survival of MCs or MC precursors, but not of increased local proliferation. Recruitment of MCs is paralleled by the expression of monocyte chemoattractant protein-1 (MCP-1), but not by other chemokines such as RANTES (regulated on activation, normal T cell expressed and secreted) and/or MIP (macrophage inflammatory protein)-1alpha/beta. Notably, 60-70% of MCs exhibited strong and selective IL-4 immunoreactivity, whereas other resident and passenger cells were rather quiescent. The data suggest that MC contribute significantly to the cytokine network of wound repair via MC-derived IL-4 and stimulation of fibroblast proliferation.
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PMID:Mast cell involvement in normal human skin wound healing: expression of monocyte chemoattractant protein-1 is correlated with recruitment of mast cells which synthesize interleukin-4 in vivo. 1064 Sep 99

Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell-mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell-mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon gamma-producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell-dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-)(v) (Kit(W)/Kit(W)(-v)) mice. T cell-dependent PMN recruitment was reduced >60% by anti-MIP-2 antibodies and >80% in mast cell-deficient Kit(W)/Kit(W)(-v) mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2-dependent PMN recruitment in Kit(W)/Kit(W)-(v) mice, whereas mast cells from TNF(-/)- mice did not. Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.
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PMID:Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. 1108 46

Tacalcitol (1,24(R)(OH)2D3, TV-02) inhibited the TPA-induced inflammatory cell infiltration (largely neutrophils) histopathologically and myeloperoxidase (MPO) activity dose-dependently. Tacalcitol inhibited the mRNA expression and protein production of TPA-induced macrophage inflammatory protein-2 (MIP-2) and KC, the functional analogue of human interleukin (IL)-8, in the skin. Immunohistochemical staining of the TPA-applied skin revealed that mast cells expressed MIP-2, whereas KC was observed in keratinocytes, fibroblasts and outer root sheath of hair follicles. Furthermore, tacalcitol inhibited TPA-induced mast cell degranulation 24 hr after application without influence on the total number of mast cells. In this study, tacalcitol was found to have an inhibitory effect on cutaneous inflammation such as inhibition of neutrophil infiltration, MIP-2 and KC production, and mast cell degranulation in TPA-treated hairless mice. These results suggest that tacalcitol modulates cutaneous inflammation as well as keratinocyte proliferation and differentiation, and the inhibitory effect of tacalcitol on cutaneous inflammation may contribute to clinical the effectiveness in the treatment of psoriasis.
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PMID:Anti-inflammatory effects of tacalcitol (1,24(R)(OH)2D3, TV-02) in the skin of TPA-treated hairless mice. 1518 40


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