Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A proportion of DBA/2 mice do not reject the large intestinal nematode parasite Trichuris muris. In this strain and the early rejecting NIH and the late rejecting CBA/Ca strains the kinetics of the mast cell accumulation in a primary infection were similar with peak mast cell numbers being recorded on day 20 post-infection. Comparisons between rejector and non-rejector DBA/2 mice showed no differences in the mast cell accumulation. There was no rise in mast cell numbers in response to a secondary infection, in either the NIH or CBA/Ca strains, for at least 3 days after the infection had been expelled. It is suggested that mucosal mast cell accumulation is not induced by a simple response to parasite factors, that the cells are not directly involved in the expulsion of T. muris and that any role they play in the spontaneous cure response is subject to more complex control.
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PMID:The use of host strain variation to assess the significance of mucosal mast cells in the spontaneous cure response of mice to the nematode Trichuris muris. 720 84

The skin is a major target organ for graft-versus-host disease (GVHD), the principal complication of allogeneic bone marrow transplantation. The purpose of the present study was to test whether mast cell degranulation might be related to early target cell injury in the development of acute GVHD. We employed two irradiated murine strain combinations, one in which disease was mediated by CD4+ effector T cells (B10.D2-->DBA/2), and the other by CD8+ effector T cells (B10.BR-->CBA). As compared to controls, both models exhibited mast cell degranulation of differing extents and patterns, as well as dyskeratosis in the epidermis before the influx of effector lymphocytes. These results suggested that factors produced and released by degranulated dermal mast cells might contribute to early target cell injury. Accordingly, the possible role of tumor necrosis factor (TNF)-alpha, a cytokine recently discovered in mast cell granules, was investigated by the injection of anti-TNF-alpha antibody during the course of disease mediated by either CD4+ or CD8+ T cells. Although overall survival of recipients undergoing CD4+ T-cell-mediated GVHD was only slightly improved and the extent of mast cell degranulation was not affected by anti-TNF-alpha antibody treatment, the skin exhibited a significant diminution in the number of dyskeratotic cells/linear mm at 3-4 weeks post-transplantation. In contrast, anti-TNF-alpha antibody failed to enhance survival or reduce the number of dyskeratotic cells in the skin during CD8+ T-cell-mediated disease. Finally, to determine whether CD8+ T-cell-mediated GVHD was at all dependent upon mast cell involvement, the C3H.SW-->B6WWv strain combination was utilized, in which recipients were genetically deficient in mast cells. Onset of GVHD was significantly delayed in B6WWv mice and was clearly correlated to the appearance and increase of de novo mast cells at later time points.
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PMID:Role of mast cells in early epithelial target cell injury in experimental acute graft-versus-host disease. 790 82

A cloned cell line was established from tumor cells spontaneously developed in a coculture of an autoreactive T cell line (1/+ T1) and 30 Gy-irradiated MRL/+ spleen cells with Con A supernatants. Morphological studies and studies of histamine content and modes of histamine release after stimulation with compound 48/80 revealed that the cell line (MRL-MC3) had mast cell characteristics. MRL-MC3 was transplantable not only to MRL/+, MRL/lpr and AKR/J (H-2k) mice but also to BALB/c and (BALB/c x DBA/2) F1 (H-2d) mice, although the allogeneic mice survived twice as long as syngeneic mice after i.v. injection. In addition, after i.v. injection, the mast cells infiltrated the livers and spleens of syngeneic (MRL/+) mice, however the lymph nodes around the mesenterium to the parapylorus in allogeneic (BALB/c) mice. A mast cell line (BALB-MC) was also established from a lymph node of MRL-MC3-injected BALB/c mice. Cell surface marker analyses revealed clear differences between the BALB-MC and the original MRL-MC3, which was positive for the expression of MHC class I antigens (K, D), I-E antigen and c-abl-encoded (anti-pEX-2 antibody-reactive) proteins, but not for I-A on the cell surface. In contrast, BALB-MC showed positive only for the MHC class I antigens (K, D) on the surface, and also positive for anti-pEX-2 antibody-reactive cytoplasmic proteins, as seen in MRL-MC3. Mast cells obtained from MRL-MC3-injected MRL/+ mice showed the same staining pattern as MRL-MC3. BALB-MC induced shorter survival times (approximately half) in both MRL/+ and BALB/c mice than MRL-MC3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transplantability and MHC antigen expression of tumor mast cells. 846 97

The murine W and Steel loci encode the Kit receptor tyrosine kinase and its ligand, Steel factor, respectively. Loss of function mutations at either the W or Sl loci lead to a variety of pleiotropic developmental defects, including mast cell deficiency and severe macrocytic anemia. In addition to these loss-of-function mutations, gain-of-function mutations in c-kit, leading to constitutive activation of the Kit receptor, have also been identified in both rodent and human mastocytomas. In this study, we have examined the transforming potential and biologic effects of a point mutation that results in substitution of the aspartic acid at codon 814 in the cytoplasmic kinase domain to tyrosine (D814Y) by introducing either wild-type (Kit) or mutant KitD814Y (KDY) cDNA into an interleukin-3-dependent mast cell line IC2. Stimulation of cells expressing the wild-type Kit receptor (IC2/Kit) with Steel factor in vitro resulted in a short-term growth response, whereas IC2/KDY cells were capable of sustained proliferation in a ligand-independent manner. In addition, expression of KDY resulted in the oncogenic transformation of IC2 cells, as determined by colony formation in vitro in the absence of exogenous growth factors and the formation of mastocytomas in vivo in syngeneic DBA/2 mice. Surprisingly, KDY expression in IC2 cells triggered dramatic changes in cell size and the extent of granulation. In addition, KDY induced the expression of mouse mast cell protease-4 (MMCP-4) and MMCP-6. In contrast, neither of these molecular or cellular changes was observed in IC2/Kit cells treated with Steel factor. These results show that the D814Y mutation in the cytoplasmic kinase domain of the Kit receptor induces ligand-independent mast cell growth in vitro, tumorigenicity in vivo, and mast cell differentiation.
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PMID:A point mutation in the catalytic domain of c-kit induces growth factor independence, tumorigenicity, and differentiation of mast cells. 860 25

Different strains of mice have varying susceptibilities to ultraviolet radiation (UV) of wavelength 280-320 nm (UVB) for 50% suppression of systemic contact hypersensitivity (CHS) responses. Prevalence of histamine-staining dermal mast cells in different strains of mice (C57BL/ 6J, DBA/2, BALB/c) correlated directly with their susceptibility to UVB-induced systemic immunosuppression. BALB/c mice carrying Uvs1, a major locus for susceptibility to UV-induced immunosuppression, contained greater numbers of dermal mast cells than BALB/c mice of the same parental origin. Strains of mice that were differentiated on their susceptibility to UVB-induced downregulation of systemic CHS responses were similar in their susceptibility to histamine-induced immunomodulation. Histamine, but not UVB irradiation, decreased systemic CHS responses in mast cell-depleted mice (W f/W f). Reconstitution of the dorsal skin of W f/W f mice with bone marrow-derived mast cell precursors from nonmutant mice rendered the mice susceptible to UVB irradiation for systemic suppression of CHS responses. UVB irradiation did not suppress delayed type hypersensitivity responses to allogeneic spleen cells in W f/W f mice. In contrast, UV irradiation suppressed CHS responses in W f/W f mice when hapten was applied to the irradiated site. This study demonstrates that dermal mast cells are necessary for the induction of systemic suppression of CHS responses by UVB radiation, and suggests that mast cell- derived histamine is one component of this UVB-induced systemic immunosuppression.
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PMID:Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice. 962 64

Uveal mast cells have previously been considered to be vital mediators of experimental uveitis. We extended the study of these cells to experimental melanin-induced uveitis (EMIU), a recently described clinically relevant model, and re-examined their role in endotoxin-induced uveitis (EIU) using genetically mast cell-depleted mice on a single background. EMIU was induced in Fischer 344 rats by immunisation with bovine ocular melanin (250 microgram. Animals were killed immediately, and on days 1 and 3 of clinical disease. Numbers of uveal mast cells and the percentage of degranulated cells were counted in whole-mount preparations. There was no significant change in either measure across the selected time points. To induce EIU, normal and mast cell-depleted DBA/2 mice were injected with Escherichia coli lipopolysaccharide (400 microgram). Cells infiltrating the eye 24 h after injection were quantified in 5 micrometer ocular cross-sections. Disease was not significantly reduced in the mast cell-depleted mutants. We conclude that uveal mast cells are not required for the development of EMIU or, in contrast to earlier work, EIU.
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PMID:Uveal mast cells are not required for rodent uveitis. 973 Nov 21

The therapeutic potential of salbutamol, a beta2-adrenergic agonist, was explored in collagen-induced arthritis. This study was based on a report that salbutamol, by elevating intracellular cAMP, inhibits IL-12 production by macrophages and dendritic cells, thus preventing Th1 development. Ten-week-old male DBA/1 mice were immunized by intradermal injection of type II collagen in CFA. Arthritis developed 15-30 days later and the mice were treated after onset of disease with salbutamol, 200 microgram i.p. After 10 days, the mice were sacrificed, and the hind paws were evaluated histologically. Salbutamol, 200 microgram daily or every other day, had a profound therapeutic effect on the clinical progression of arthritis, as assessed by clinical score and paw thickness. The therapeutic effect was dose dependent. Daily administration of 200 microgram of salbutamol offered the best protection against joint damage, as assessed by histology. In vitro, salbutamol reduced IL-12 and TNF-alpha release by peritoneal macrophages in a dose-dependent manner, as well as TNF release by synovial cells from arthritic mice. Ex vivo, draining lymph node cells of the salbutamol-treated arthritic mice showed a diminished CII-specific IFN-gamma production and proliferation. In vivo, salbutamol specifically blocked mast cell degranulation in joint tissues. In conclusion, salbutamol has important effects on the immunoinflammatory response and a significant therapeutic action in collagen-induced arthritis.
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PMID:The beta2-adrenergic agonist salbutamol is a potent suppressor of established collagen-induced arthritis: mechanisms of action. 1022 75

Differences in dermal mast cell prevalence for adult mice of different strains have been reported previously. In this study, the dermal mast cell prevalence for BALB/c and C57BL/6 mice at 6 weeks of age was similar but as BALB/c mice matured from 6 to 10 weeks of age, their dermal mast cell prevalence halved. In contrast, there was no significant difference in the dermal mast cell prevalence of 6- and 10-week-old C57BL/6 mice. These differences determined the degree of susceptibility of BALB/c and C57BL/6 mice of different ages to UVB (UV radiation of wavelength 280-320 nm)-induced systemic immunosuppression. Expression of the receptor for stem cell factor, Kit protein, was examined on mast cells under conditions in which the dermal mast cell prevalence varied. A significant correlation was observed between Kit expression by mast cells from adult BALB/c, DBA/2 and C57BL/6 mice and dermal mast cell prevalence. In BALB/c mice, mast cell Kit expression decreased as the mice matured from 6 to 10 weeks of age and correlated with the reduction in dermal mast cell numbers. Kit levels on dermal mast cells from C57BL/6 mice were consistently higher than on mast cells from BALB/c mice although significant reductions in Kit were also measured with ageing from 6 to 10 weeks. We hypothesize that regardless of the extent of Kit expression, the dermal mast cell populations were maximally expanded in C57BL/6 mice. We suggest that BALB/c mice of 6 and 10 weeks of age are useful hosts in which to quantitatively evaluate mast cell involvement in a range of functional assays involving skin.
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PMID:Age-related changes in dermal mast cell prevalence in BALB/c mice: functional importance and correlation with dermal mast cell expression of Kit. 1058 93

This study examined the gene expression of mouse mast cell proteases to clarify their role in the pathophysiology of viral myocarditis. Male DBA/2 mice were inoculated intraperitoneally with the encephalomyocarditis virus and the gene expression of mast cell chymase, mouse mast cell protease (mMCP)-4 and -5, and tryptase, mMCP-6, matrix metalloproteinase (MMP)-9 and type-I procollagen was measured by real-time quantitative RT-PCR analysis. The gene expression of mMCP-4, -5 and -6 mRNA was increased at 5 days, and continued to increase to day 14, coinciding with a prominent inflammatory reaction and extensive myocardial necrosis and fibrosis. The gene expression of MMP-9 was also increased, and there was a significant correlation between upregulation of mast cell proteases and MMP-9. The gene expression of type-I procollagen was increased at 5 days and continued to increase to day 14, suggesting that a fibrotic process had already begun during the acute stage of viral myocarditis. These findings suggest that mast cell chymase and tryptase participate in the acute inflammation and remodeling process of viral myocarditis.
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PMID:Gene expression of cardiac mast cell chymase and tryptase in a murine model of heart failure caused by viral myocarditis. 1457 24

BACKGROUND: Ischaemia reperfusion (IR) injury of skeletal muscle, is a significant cause of morbidity following trauma and surgical procedures, in which muscle fibre types exhibit different susceptibilities. The relative degree of mast cell mediated injury, within different muscle types, is not known. METHODS: In this study we compared susceptibility of the fast-twitch, extensor digitorum longus (EDL), mixed fast/slow-twitch gastrocnemius and the predominately slow-twitch soleus, muscles to ischemia reperfusion (IR) injury in four groups of mice that harbour different mast cell densities; C57/DBA mast cell depleted (Wf/Wf), their heterozygous (Wf/+) and normal littermates (+/+) and control C57BL/6 mice. We determined whether susceptibility to IR injury is associated with mast cell content and/or fibre type and/or mouse strain. In experimental groups, the hind limbs of mice were subjected to 70 minutes warm tourniquet ischemia, followed by 24 h reperfusion, and the muscle viability was assessed on fresh whole-mount slices by the nitroblue tetrazolium (NBT) histochemical assay. RESULTS: Viability was remarkably higher in the Wf/Wf strain irrespective of muscle type. With respect to muscle type, the predominately slow-twitch soleus muscle was significantly more resistant to IR injury than gastrocnemius and the EDL muscles in all groups. Mast cell density was inversely correlated to muscle viability in all types of muscle. CONCLUSION: These results show that in skeletal muscle, IR injury is dependent upon both the presence of mast cells and on fibre type and suggest that a combination of preventative therapies may need to be implemented to optimally protect muscles from IR injury.
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PMID:The role of mast cells and fibre type in ischaemia reperfusion injury of murine skeletal muscles. 1581 78


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