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)

Genetic association of some immune-mediated human uveitic diseases with histocompatibility antigens, ethnic origin, familial background, or gender have suggested the presence a hereditary component in susceptibility. Experimental autoimmune uveoretinitis (EAU) can be induced in inbred rodents by immunization with evolutionarily conserved retinal proteins, and mimics many features of human uveitis. Susceptibility to EAU is genetically controlled, and the model is being used to study mechanisms that might affect susceptibility to ocular autoimmune disease. EAU expression in mice and in rats requires the presence of both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility in H-2k mice was tentatively mapped to the I-A subregion (HLA-DR equivalent), implicating epitope recognition as a major mechanism in susceptibility. In contrast, expression of the I-Ek gene product (HLA-DQ equivalent) appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include regulation of responses to lymphokines, hypothalamic-adrenal-pituitary axis hormones, mast cell/vascular effects, and possibly the T cell repertoire. The data are interpreted to suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background. These results might help to explain why only a minority of individuals with a susceptible HLA type develop uveitis, as well as the variable incidence of disease in HLA-identical populations of different ethnic backgrounds.
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PMID:Immunogenetic aspects of clinical and experimental uveitis. 129 Jul 50

Circulating histamine-releasing factors have been identified in the serum and plasma of chronic-urticaria patients by in vivo skin testing and in vitro histamine release from heterologous mixed leukocytes. Quantitative mast cell studies of serum skin test biopsies and electron microscopy indicate that the serum factors release histamine by mast cell degranulation. Peripheral blood basophils and total cellular blood histamine are reduced in chronic-urticaria patients suggesting that the circulating serum factors cause sustained degranulation. Histamine-releasing activity has been identified by skin testing in ultrafiltered serum fractions less than 30 kDa and greater than 100 kDa. In vitro histamine-releasing activity was confined to ultrafiltered serum fractions greater than 100 kDa and was present in IgG purified from some chronic-urticaria sera by protein G affinity chromatography. The dose-response relationship and kinetics of histamine release in vitro were similar to those of anti-human IgE. 'Desensitisation' of basophils by prior incubation with anti-IgE in the absence of calcium and competitive inhibition studies with myeloma IgE serum indicated that histamine-releasing autoantibodies in chronic-urticaria sera and purified IgG have the properties of anti-IgE. Plasma exchange in 4 patients with active chronic urticaria refractory to antihistamine therapy showing in vivo and in vitro histamine-releasing activity was followed by temporary remission of disease activity in 2 of them. It is possible that chronic urticaria is an autoimmune disease.
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PMID:Histamine-releasing autoantibodies in chronic urticaria. 172 16

Experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease can be transferred with lymphoid cells from actively immunized rats into naive recipients. In the mouse, previous studies have suggested a role for histamine/serotonin in the development of active EAE. We have found that myelin basic protein-reactive cells transfer a biphasic skin test response to naive rats analogous to what has been described in the mouse contact dermatitis system, where mast cell sensitization by Ag-specific T cell factors is required for the induction of skin test responses. Treatment of cell recipients with the serotonin receptor antagonists, cyproheptadine or methysergide, blocked or significantly reduced the development of EAE. Furthermore, it was found that treatment with cyproheptadine was effective in blocking clinical disease when administered day 3 to day 6 after cell transfer. In contrast, cyproheptadine treatments before induction of paralysis day 0 to 3, failed to alter the course of clinical disease. The inhibitor of mast cell degranulation, proxicromil, was also found to effectively block the elicitation of adoptively transferred EAE and was also found to be effective when administered just before the onset of clinical disease. Reserpine, a compound known to deplete mast cells of vasoactive amines by forcing granule contents into the cytoplasm where they are degraded by cell enzymes, was also effective in blocking both active and adoptively transferred EAE. Disease inhibition was found to be partially reversed with pargyline, an inhibitor of monoamine oxidase. In addition lymphocytes from treated animals were capable of transferring disease to naive recipients and appeared to have normal activity as assessed by Ag-or mitogen-driven proliferation in addition to IL-2 production.
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PMID:The role of mast cells in the elicitation of experimental allergic encephalomyelitis. 246 41

Experimental autoimmune uveoretinitis (EAU) is an ocular autoimmune disease induced in rats by immunization with retinal S-antigen. Athymic nude rats (rnu/rnu) have been previously shown to be refractory to EAU induction and antibody production to S-antigen, while heterozygous (rnu/+) are good responders. Increasing the antigen dose and adding pertussis adjuvant produced ocular disease in some nude rats, and antibody response in most of them. Specific IgE antibodies were demonstrated by ELI-SA only in the serum of nude rats presenting the disease. However, most immunized nude rats had evidence of mast cell sensitization to S-antigen (direct degranulation test) and of circulating specific IgE detected by passive sensitization of normal mast cells (indirect degranulation test). This positive response could be explained by an incomplete depletion of the different T lymphocyte subsets.
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PMID:Experimental autoimmune uveoretinitis in athymic rats: specific IgE response to retinal S-antigen and disease. 387 39

An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.
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PMID:An association between susceptibility to experimental autoimmune uveitis and choroidal mast cell numbers. 633 30

The initiation of a humoral immune response to a foreign antigen is a complex biologic process involving the interaction of many cell types and their secreted products. Autoimmune diseases, which are characterized by an abnormal activation of the immune system, probably result from the failure of normal self-tolerance mechanisms. The etiology of such illnesses, however, is far from being understood. While there have been extensive studies on the participation of the immune and endocrine systems in autoimmune diseases, few have dealt with nervous system-mediated immunoregulation in such situations. Evidence continues to grow suggesting that nerve growth factor (NGF), first identified for its activity in promoting the growth and differentiation of sensory and sympathetic neurons, may exert a modulatory role on neuroimmunoendocrine functions of vital importance in the regulation of homeostatic processes. Newly detected NGF-responsive cells belong to the hemopoietic-immune system and to populations in the brain involved in neuroendocrine functions. NGF levels are elevated in a number of autoimmune states, along with increased accumulation of mast cells. NGF and mast cells both appear to be involved in neuroimmune interactions and tissue inflammation. Moreover, mast cells themselves synthesize, store, and release NGF, proposing that alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature. This review focuses on these cellular events and presents a working model which attempts to explain the close interrelationships of the neuroendocrinoimmune triade via a modulatory action of NGF.
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PMID:Nerve growth factor and autoimmune diseases. 777 4

We studied the histological modifications in the accessory glands of autoimmune rats. Adult male Wistar rats were id immunized three times with saline extract of rat male accessory glands (RAG) chemically modified (MRAG) in complete Freund's adjuvant (CFA) (groups 1, 2, and 3). Prior to the first immunization with MRAG-CFA groups 2 and 3 received peritoneal cells obtained from rats that had been injected 2 or 24 hr previously with low doses of RAG. Furthermore, an additional group (group 4) ip immunized with liposome-associated-RAG was incorporated. The delayed-type hypersensitivity response studied 10 or 15 days after first immunization was positive for rats of groups 1, 3, and 4, while it was negative for rats of group 2. Serum samples obtained on Day 45 and studied by ELISA showed high levels of autoantibodies in groups 1 and 2 and lower levels of autoantibodies in group 3, but did not show autoantibodies in group 4. The histological studies performed 10 days after the last immunization showed organ-specific lesions in the accessory glands in animals of groups 1, 3, and 4. Infiltration of mononuclear cells was the main alteration in group 1, while infiltration of mast cells and polymorphonuclear leukocytes were present in specimens of groups 3 and 4. The main finding of this study was a significant increase (P < 0.0005) in the extent of mast cell degranulation in the specimens of accessory glands stained with toluidine blue. Our results suggest that mast cells are activated in our experimental model of autoimmune disease.
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PMID:Mast cells in accessory glands of experimentally induced prostatitis in male Wistar rats. 785 13

Histamine is unique in being the only substance described to date which fulfils all of the criteria established by Dale for an inflammatory mediator. Thus, histamine is known to cause the "Triple Response" of Lewis and to act via H1 and H2 receptors to produce vasodilation and increased vascular permeability; elevated levels of histamine are found in inflamed tissue; histamine is produced and stored in mast cells and there are established mechanisms for histamine release via mast cell surface receptors; and antihistamines alleviate the clinical manifestations of histamine release. There have been several recent advances in our understanding of histamine pharmacology and of the pathomechanisms of chronic idiopathic urticaria (CIU), a disease in which histamine plays an important role. Two new histamine receptors have been identified, the inhibitory (H3) receptor and the intracellular (H(ic)) receptor involved in cell proliferation. There is now evidence that mast cell derived histamine release in patients with CIU is due to an autoimmune disease, mediated by autoantibodies to the alpha-subunit of the high affinity IgE receptor on mast cells and basophils. Removal of these autoantibodies by plasmapheresis, or treatment with intravenous immunoglobulins may cause clinical remission. Cyclosporin A has also been found to be of benefit to some patients with CIU probably due to a mast cell "stabilising" effect, leading to reduced release of histamine and other mediators. This article reviews our current knowledge on histamine, its role, receptors and mechanisms for release.
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PMID:Histamine: the quintessential mediator. 899 Jun 94

Until relatively recently, the pathophysiologic significance of the recognized associations between autoimmunity and swelling was largely unknown. It has now become clear that autoimmunity can play a critical role in the pathogenesis of chronic urticaria and acquired C1-INH deficiency with angioedema. Chronic urticaria has been associated with antithyroid autoantibodies, anti-IgE autoantibodies, and anti-Fc epsilon RI autoantibodies. The latter two autoantibodies are particularly interesting in that they have been shown to be capable of directly causing mast cell degranulation. It appears likely, therefore, that most cases of chronic urticaria will ultimately be considered an autoimmune disease rather than an allergic disease. The link between autoimmunity and the development of acquired C1-INH deficiency is also of interest. Recent studies suggest that the majority of acquired C1-INH deficiency patients have anti-C1-INH autoantibodies that appear to be responsible for the development of the C1-INH deficiency. In addition, both chronic urticaria and C1-INH deficiency can be associated with other autoimmune diseases, although the importance of these associations remains to be determined. Recognition of the role of autoantibodies in the pathogenesis of chronic urticaria and acquired C1-INH deficiency has altered the range of diagnostic and therapeutic approaches that need to be considered in approaching patients with chronic urticaria or acquired C1-INH deficiency. Future progress in understanding the genesis of these diseases may help elucidate the mechanism of autoantibody generation.
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PMID:Urticaria, angioedema, and autoimmunity. 931 73

Primary sclerosing cholangitis (PSC) is characterized by destructive inflammation and fibrosis affecting the bile ducts. The etiology of PSC is still unknown, although lymphocytic infiltration in the portal areas suggests an immune-mediated destruction of the bile ducts. Patients with one autoimmune disease often suffer from one or more other autoimmune diseases. It is well known that there is a close relationship between PSC and inflammatory bowel disease, particularly ulcerative colitis(UC). However, the pathological findings in UC and other overlap diseases do not resemble those of PSC. In the present study, we report a patient with chronic sclerosing sialadenitis (Kuttner's tumor) and PSC. It is compared the sclerosing changes in both salivary glands and bile ducts histologically. In addition, the expression pattern of mast cell tryptase, b-FGF, and HLA-DR were examined in both tissues immunohistochemically. Histological features of sclerosing change in both salivary and bile ducts were quite similar. Marked mast cell infiltration and b-FGF expression were seen in the sclerosing areas in both tissues. In active inflammatory areas of the salivary glands, HLA-DR expression was also seen. We hypothesized that similar immune reactions occur in both the salivary gland and bile ducts and are responsible for the fibrosis that follows.
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PMID:Immunological similarities between primary sclerosing cholangitis and chronic sclerosing sialadenitis: report of the overlapping of these two autoimmune diseases. 1071 53


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