UNIPROT:P15088 - FACTA Search

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

Bleomycin induces local inflammatory process with subsequent pulmonary fibrosis. An unknown chemoattractant induces the mast cell (MC) migration to the injured lung tissue. Aim of this study was evaluation of the number, topography and ultrastructure (TEM) of the MC in rat lungs with bleomycin-induced fibrosis. The bleomycin was administered once intratracheally (3.6 mg/kg). The animals were sacrificed on 7th. 14th and 21st day of experiment. MC were stained with Csaba's method. An evident increase in MC number related to the phase of experiment and stage of lung fibrosis was observed: 520, 1200, 4745 per cm2 section on the 7th, 14th and 21st day respectively. In control the MC number was 163 per cm2 section (p < 0.001). On the 7th day the MC were rich in red granules (mature granules with preponderance of heparin). They were located mainly in pleura and around the blood vessels, as in control. On the 14th and 21st day the majority of MC was situated in places of active fibrosing. They contained exclusively blue granules (the young granules with preponderance of biogenic amines), mixture of increased secretory function of the MC in the fibrotic lungs. Some of the MC granules showed fusion and altered matrix contents, other were emptied in piecemeal manner. A net of microtubules connected the granules was observed. Degranulation of MC may release heparin and cytokines able to stimulate synthesis of extracellular matrix. It has been suggested that heparin contributes to the fibrotic process and angiogenesis, stimulating directly or indirectly collagen synthesis by binding, stabilization and activation of fibroblast growth factor (FGF) and cell adhesion glycoproteins.
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PMID:[Morphology of mast cells in experimental pulmonary fibrosis induced with bleomysin]. 864 Jan 54

We showed previously that autosomal recessive determinants control the development of pulmonary fibrosis in mice during the early and late phases after irradiation. The extent of fibrosis was inversely correlated with the intrinsic lung activity of both plasminogen activator (PLA) and angiotensin-converting enzyme (ACE). To test these observations further, two groups of mice were given a dose of 15 Gy to the thorax: offspring of a backcross between C57L/J ("fibrosing mice") and the F1 of CBA/J ("non-fibrosing in the early phase") x C57L/J, and additional F1 individuals of CBA/J x C57L/J. Mice were euthanized upon developing a substantial respiratory deficiency (50% reduction in carbon monoxide uptake) during the early phase (14-25 weeks postirradiation). Seventeen mice from the backcross were heavily fibrosed, 38 were classed as intermediate, and 15 contained no fibrosis. No evidence of sex linkage was seen. These data strongly support our earlier conclusions and suggest that two autosomal genes which function additively determine the extent of the principal type of fibrosis in these strains. As no indication of a bimodal distribution of lung PLA or ACE activity was obtained, it is unlikely that one of the genes controls the level of either enzyme. The F1 mice unexpectedly showed small amounts of an unusual type of fibrosis which was not associated with hyaline material or fibrin deposits, in contrast to all previous reports of fibrosis during the early phase in mice. Similar, fibrin-free fibrosis was found during the early phase in mast cell-deficient WBB6F1/J mice (and their normal siblings). In the F1 mice this unusual fibrosis appears to be regulated independently by two additional genes, one of which is sex-linked.
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PMID:Evidence for two patterns of inheritance of sensitivity to induction of lung fibrosis in mice by radiation, one of which involves two genes. 867

Human interleukin 13 (IL-13) is a cytokine that has a profound effect on primary immune cells by inducing immunoglobulin production, proliferation of B cells, and the differentiation of cells of the monocytic lineage. IL-13 can inhibit the production of inflammatory cytokines by both macrophages and monocytes. Previously, IL-13 expression has been reported only in cells of the T-cell lineage and the mast cell line HMC-1. We now report the presence of IL-13 mRNA and protein in human alveolar macrophages (AMs) analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunoabsorbent assay (ELISA), respectively, and IL-13 protein in bronchoalveolar lavage fluid (BALF) of subjects with pulmonary fibrosis. We have investigated 13 patients from 49 to 75 yr of age with forms of pulmonary fibrosis, and eight healthy volunteers from 24 to 61 yr of age. Their AMs were obtained by bronchoalveolar lavage (BAL) and purified by adherence. The proportion of BAL purified AMs expressing IL-13 mRNA was increased in those subjects with fibrotic lung disease, in comparison with those from control subjects (11 of 13 versus 2 of 8, P < 0.01). IL-13 protein was detectable in the BALF of 8 of 13 patients with pulmonary fibrosis, but in none of the control subjects. AMs of four subjects with systemic sclerosis were cultured and IL-13 protein was increased in the culture supernatants when compared to the control subjects, although this did not reach significance. These findings show that IL-13 mRNA is not only a product of T cells, but is also expressed in both normal AMs and those from subjects with pulmonary fibrosis, and that at least some of the IL-13 mRNA is translated into protein and secreted in subjects with pulmonary fibrosis. We hypothesize that IL-13 may be expressed by normal human AMs as part of the homeostatic control process but its production may be increased in the presence of inflammatory lung disease.
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PMID:Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. 944 46

Anaphylaxis represents an extreme form of allergic reaction. This acute-phase component of allergy and asthma is triggered by allergen-induced degranulation of mast cells following the cross-linking of cell surface-bound, allergen-specific IgE, resulting in the liberation of inflammatory mediators and the development of bronchoconstriction. We used IL-13 transgenic mice to investigate the role of this Th2 cell-derived cytokine in the onset of allergic disease. Strikingly, IL-13-transgenic mice were highly predisposed to fatal anaphylaxis following Ag sensitization. This response correlated with substantially elevated levels of circulating Ag-specific IgE, mast cell degranulation, and histamine release. Furthermore, allergen exposure also induced phenotypic changes typical of asthma, including pulmonary fibrosis, goblet cell hyperplasia, elevated Th2 cytokines, eosinophilia, and airways occluded by mucus and Charcot-Leyden crystals. Expression of IL-4 was not required for the induction of IgE-mediated responses. These data represent the first characterization of a functional role for IL-13-induced IgE in the generation of immediate hypersensitivity reactions and highlight the importance of IL-13 in the development of the symptoms of atopy. The systemic regulation of this response makes these mice an important resource for studying atopic responses.
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PMID:IL-13 overexpression predisposes to anaphylaxis following antigen sensitization. 1116 Mar 36

Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide variety of mediators. They develop from bone marrow-derived progenitor cells, primed with stem cell factor (SCF), which mediates its actions by interacting with the SCF receptor or c-kit on the cell surface. Mast cells continue their maturation and differentiation in peripheral tissue, developing into two well described subsets of cells, MCT and MCTC cells, varying in content of tryptase and chymase as well as in immunobiology. Mast cells are activated by numerous stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI), superoxides, complement proteins, neuropeptides and lipoproteins resulting in activation and degranulation. Following activation, these cells express mediators such as histamine, leukotrienes and prostanoids, as well as proteases, and many cytokines and chemokines, pivotal to the genesis of an inflammatory response. Recent data suggests that mast cells may play an active role in such diverse diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis. Mast cells directly interact with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been demonstrated to have inhibitory effects on mast cell degranulation or mediator release.
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PMID:The human mast cell: functions in physiology and disease. 1153 8

Basic fibroblast growth factor (bFGF) is a potent mitogenic factor for smooth muscle cells, myofibroblasts, and fibroblasts, proliferation of which is a hallmark of idiopathic pulmonary fibrosis (IPF) and lymphangioleiomyomatosis (LAM). Mast cells produce bFGF and have been associated with pulmonary fibrosis. We hypothesize that smooth muscle cell/myofibroblast-like cells will be spatially associated with bFGF-containing mast cells and that bFGF receptors will be expressed on the effector cells in IPF and LAM. We performed quantitative immunohistochemistry for bFGF, mast cell tryptase, smooth muscle actin for smooth muscle cell/myofibroblast-like cells, and fibroblast growth factor receptors (Flg, Bek) and measured collagen and elastic fiber in lung sections from IPF (n = 14), LAM (n = 9), and control lung (n = 10). IPF and LAM lung contained more smooth muscle cell/myofibroblast-like cells than did control lung. bFGF-containing mast cells were abundant both in IPF and LAM and were associated with collagen, elastic fibers, and smooth muscle cell/myofibroblast-like cells in IPF. Flg was expressed on epithelial cells, endothelial cells, smooth muscle cell/myofibroblast-like cells, and macrophages in IPF. In LAM, Flg was expressed on epithelial cells adjacent to smooth muscle cell/myofibroblast-like cell aggregates. Bek was expressed dominantly on smooth muscle cell/myofibroblast-like cells in LAM and on smooth muscle cell/myofibroblast-like cells as well as neutrophils in IPF. These data suggest that mast cell-derived bFGF might exert fibrogenic, proliferative effects on smooth muscle cell/myofibroblast-like cells through its receptors.
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PMID:Basic fibroblast growth factor and its receptors in idiopathic pulmonary fibrosis and lymphangioleiomyomatosis. 1220 79

Mast cells are fascinating, multifunctional, tissue-dwelling cells that have been traditionally associated with the allergic response. However, recent studies suggest these cells may be capable of regulating inflammation, host defense, and innate immunity. The purpose of this review is to present salient aspects of mast cell biology in the context of mast cell function in physiology and disease. After their development from bone marrow-derived progenitor cells that are primed with stem cell factor, mast cells continue their maturation and differentiation in peripheral tissue, developing into two well-described subsets of cells, MC(T) and MC(TC) cells. These cells can be distinguished on the basis of their tissue location, dependence on T lymphocytes, and their granule contents. Mast cells can undergo activation by antigens/allergens, superoxides, complement proteins, neuropeptides, and lipoproteins. After activation, mast cells express histamine, leukotrienes, and prostanoids, as well as proteases, and many cytokines and chemokines. These mediators may be pivotal to the genesis of an inflammatory response. By virtue of their location and mediator expression, mast cells may play an active role in many diseases, such as allergy, parasitic diseases, atherosclerosis, malignancy, asthma, pulmonary fibrosis, and arthritis. Recent data also suggest that mast cells play a vital role in host defense against pathogens by elaboration of tumor necrosis factor alpha. Mast cells also express the Toll-like receptor, which may further accentuate their role in the immune-inflammatory response. This chapter summarizes the many well-known and novel functional aspects of human mast cell biology and emphasizes their unique role in the inflammatory response.
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PMID:The human mast cell: an overview. 1611 Jan 46

The mast cell has been a fundamental focus for nearly half a century in the effort to understand the biology of the cysteinyl leukotrienes (cysLTs). My initial interest in the cysLTs, once termed the slow reacting substance of anaphylaxis (SRS-A), was based on the findings of others that this activity was elaborated by lung tissue and constricted bronchial smooth muscle in the presence of an antihistamine. We now know that leukotriene C4 (LTC4) is formed when arachidonic acid is cleaved from membrane phospholipids, and metabolized to an epoxide intermediate, LTA4 that in turn is conjugated to reduced glutathione by an integral membrane protein, LTC4 synthase. The LTC4 is exported in an energy-dependent step and subjected to extracellular cleavage of the glutamic acid and then the glycine to provide LTD4 and LTE4, respectively. Mice with targeted disruption of the LTC4S gene are partially protected against plasma leakage elicited in the ear by adaptive immune mast cell activation or in the peritoneal cavity by microbial carbohydrate stimulation of the macrophages. Such mice are also partially protected against pulmonary fibrosis after intratracheal administration of bleomycin. A strain with targeted disruption of the CysLT1 receptor gene is protected against the pathobiological insults that augment microvascular permeability, whereas a strain with targeted disruption of the CysLT2 receptor gene is protected against pulmonary fibrosis. Thus, the expression of these receptors on endothelium, smooth muscle and cells of the haematopoietic lineage such as mast cells, macrophages, and granulocytes extends the possible role of this lipid mediator pathway to both acute and chronic inflammation.
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PMID:The mast cell and the cysteinyl leukotrienes. 1660 34

Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It has been suggested that mast cells play a role in these conditions. How mast cells would influence pathology is unknown. We thus explored mast cell interactions with silica in vitro and in B6.Cg-kit(W-sh) mast cell-deficient mice. B6.Cg-kit(W-sh) mice did not develop inflammation or significant collagen deposition after instillation of silica, while C57Bl/6 wild-type mice did have these findings. Given this supporting evidence of a role for mast cells in the development of silicosis, we examined the ability of silica to activate mouse bone marrow-derived mast cells (BMMC), including degranulation (beta-hexosaminidase release); production of reactive oxygen species (ROS) and inflammatory mediators; and the effects of silica on Fc epsilon RI-dependent activation. Silica did not induce mast cell degranulation. However, TNF-alpha, IL-13, monocyte chemotactic protein-1, protease activity, and production of ROS were dose-dependently increased after silica exposure, and production was enhanced after Fc epsilon RI stimulation. This mast cell activation was inhibited by anti-inflammatory compounds. As silica mediates some effects in macrophages through scavenger receptors (SRs), we first determined that mast cells express scavenger receptors; then explored the involvement of SR-A and macrophage receptor with colleagenous structure (MARCO). Silica-induced ROS formation, apoptosis, and TNF-alpha production were reduced in BMMC obtained from SR-A, MARCO, and SR-A/MARCO knockout mice. These findings demonstrate that silica directs mast cell production of inflammatory mediators, in part through SRs, providing insight into critical events in the pathogenesis and potential therapeutic targets in silicosis.
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PMID:Silica-directed mast cell activation is enhanced by scavenger receptors. 1690 92

Mast cells play a significant role in the pathophysiology of many diverse diseases such as asthma and pulmonary fibrosis. Ca2+ influx is essential for mast cell degranulation and release of proinflammatory mediators, while Mg2+ plays an important role in cellular homeostasis. The channels supporting divalent cation influx in human mast cells have not been identified, but candidate channels include the transient receptor potential melastatin (TRPM) family. In this study, we have investigated TRPM7 expression and function in primary human lung mast cells (HLMCs) and in the human mast cell lines LAD2 and HMC-1, using RT-PCR, patch clamp electrophysiology, and RNA interference. Whole cell voltage-clamp recordings revealed a nonselective cation current that activated spontaneously following loss of intracellular Mg2+. The current had a nonlinear current-voltage relationship with the characteristic steep outward rectification associated with TRPM7 channels. Reducing external divalent concentration from 3 to 0.3 mM dramatically increased the size of the outward current, whereas the current was markedly inhibited by elevated intracellular Mg2+ (6 mM). Ion substitution experiments revealed cation selectivity and Ca2+ permeability. RT-PCR confirmed the presence of mRNA for TRPM7 in HLMC, LAD2, and HMC-1 cells. Adenoviral-mediated knockdown of TRPM7 in HLMC with short hairpin RNA and in HMC-1 with short interfering RNA markedly reduced TRPM7 currents and induced cell death, an effect that was not rescued by raising extracellular Mg2+. In summary, HLMC and human mast cell lines express the nonselective cation channel TRPM7 whose presence is essential for cell survival.
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PMID:Functional transient receptor potential melastatin 7 channels are critical for human mast cell survival. 1778 43

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