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

Immune responses of mast cell-deficient WBB6F1-W/Wv mice and their mast cell-sufficient littermates (LM: WBB6F1-W/+, Wv/+ and +/+) were compared. After a single intravenous injection of sheep erythrocytes (SE), polyvinylpyrrolidone or bacterial lipopolysaccharide, the antigen-specific IgM plaque-forming cell (PFC) response of W/Wv mice was similar to or greater than the response of LM mice. When both primary and secondary injections of SE or chicken gamma-globulin were given to mice and antigen-specific IgG PFC responses quantified, the response of W/Wv again was similar to or greater than that of LM mice. Serum titers of antigen-specific IgE were higher in W/Wv than in LM mice after injections of ovalbumin in alum or infections of Nippostrongylus brasiliensis. Ovalbumin-sensitized W/Wv and LM mice developed active systemic anaphylaxis after ovalbumin challenge. The ability of W/Wv mice to be sensitized for and elicit contact sensitivity (CS) reactions was studied using picryl chloride or dinitrofluorobenzene as sensitizing and challenge agents and quantifying 24-hour reactions by change in ear thickness. SE or methylated bovine serum albumin was used to sensitize and challenge mice for delayed-type hypersensitivity (DTH) reactions which were quantified at 24 h by change in foot pad or ear thickness. CS and DTH reactions of W/Wv and LM mice were similar. No evidence of immune deficiency of W/Wv mice was found.
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PMID:Immune response potential of mast cell-deficient W/Wv mice. 351 77

Activated mast cells (MC) can produce a wide variety of potent inflammatory mediators. Excessive alcohol consumption is known to lead to immune deficiency and propensity for pneumonias in particular. As MCs are important in the first line of defence of mucosal membranes we have studied the effect of ethanol (EtOH) on several MC functions. EtOH attenuated dose dependently IgE-induced degranulation of mouse bone marrow derived mast cells (mBMMC) as reflected by the release of granule associated beta-hexosaminidase (beta-hex). A mean of 26 +/- 7% inhibition of beta-hex release was observed in the presence of 5/1000 (86 mM) EtOH and nearly complete inhibition in the presence of 20/1000 (344 mM) ethanol. The IgE-induced degranulation of mBMMC cultured with EtOH for seven days was inhibited to a similar degree as the degranulation of mBMMC exposed to EtOH for only one hour. Inclusion of 5/1000 (86 mM) ethanol in the medium reduced tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 production in human mast cell line (HMC-1) cells by 55 +/- 7% and 19 +/- 5%, respectively, and the presence of 20/1000 (344 mM) ethanol inhibited the expression 81 +/- 12% and 59 +/- 14% respectively. These results suggest that, in contrast to previous assumption, ethanol inhibits several critical MC functions at least in vitro. This inhibition of mediator, and cytokine release in particular, could contribute to the immune deficiency associated with chronic alcohol consumption.
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PMID:Ethanol inhibits IgE-induced degranulation and cytokine production in cultured mouse and human mast cells. 1110 96

Secondary sclerosing cholangitis (SSC) is a disease that is morphologically similar to primary sclerosing cholangitis (PSC) but that originates from a known pathological process. Its clinical and cholangiographic features may mimic PSC, yet its natural history may be more favorable if recognition is prompt and appropriate therapy is introduced. Thus, the diagnosis of PSC requires the exclusion of secondary causes of sclerosing cholangitis and recognition of associated conditions that may potentially imitate its classic cholangiographic features. Well-described causes of SSC include intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis. However, a wide variety of other associations have been reported recently, including autoimmune pancreatitis, portal biliopathy, eosinophillic and/or mast cell cholangitis, hepatic inflammatory pseudotumor, recurrent pyogenic cholangitis, primary immune deficiency, and AIDS-related cholangiopathy. This article offers a comprehensive review of SSC.
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PMID:Sclerosing cholangitis: a focus on secondary causes. 1705 22

In cells of the immune system that are stimulated by antigen or antigen-antibody complexes, Ca(2+) entry from the extracellular medium is driven by depletion of endoplasmic reticulum Ca(2+) stores and occurs through specialized store-operated Ca(2+) channels known as Ca(2+)-release-activated Ca(2+) (CRAC) channels. The process of store-operated Ca(2+) influx is essential for short-term as well as long-term responses by immune-system cells. Short-term responses include mast cell degranulation and killing of target cells by effector cytolytic T cells, whereas long-term responses typically involve changes in gene transcription and include T and B cell proliferation and differentiation. Transcription downstream of Ca(2+) influx is in large part funneled through the transcription factor nuclear factor of activated T cells (NFAT), a heavily phosphorylated protein that is cytoplasmic in resting cells, but that enters the nucleus when dephosphorylated by the calmodulin-dependent serine/threonine phosphatase calcineurin. The importance of the Ca(2+)/calcineurin/NFAT signalling pathway for lymphocyte activation is underscored by the finding that the underlying defect in a family with a hereditary severe combined immune deficiency (SCID) syndrome is a defect in CRAC channel function, store-operated Ca(2+) entry, NFAT activation and transcription of cytokines, chemokines and many other NFAT target genes whose transcription is essential for productive immune defence. We recently used a two-pronged genetic approach to identify Orai1 as the pore subunit of the CRAC channel. On the one hand, we initiated a positional cloning approach in which we utilised genome-wide single nucleotide polymorphism (SNP) mapping to identify the genomic region linked to the mutant gene in the SCID family described above. In parallel, we used a genome-wide RNAi screen in Drosophila to identify critical regulators of NFAT nuclear translocation and store-operated Ca(2+) entry. These approaches, together with subsequent mutational and electrophysiological analyses, converged to identify human Orai1 as a pore subunit of the CRAC channel and as the gene product mutated in the SCID patients.
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PMID:Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytes. 1757 87

A significant number of contributions to our understanding of primary immunodeficiencies (PIDs) in pathogenesis, diagnosis, and treatment were published in the Journal in 2013. For example, deficiency of mast cell degranulation caused by signal transducer and activator of transcription 3 deficiency was demonstrated to contribute to the difference in the frequency of severe allergic reactions in patients with autosomal dominant hyper-IgE syndrome compared with that seen in atopic subjects with similar high IgE serum levels. High levels of nonglycosylated IgA were found in patients with Wiskott-Aldrich syndrome, and these abnormal antibodies might contribute to the nephropathy seen in these patients. New described genes causing immunodeficiency included caspase recruitment domain 11 (CARD11), mucosa-associated lymphoid tissue 1 (MALT1) for combined immunodeficiencies, and tetratricopeptide repeat domain 7A (TTC7A) for mutations associated with multiple atresia with combined immunodeficiency. Other observations expand the spectrum of clinical presentation of specific gene defects (eg, adult-onset idiopathic T-cell lymphopenia and early-onset autoimmunity might be due to hypomorphic mutations of the recombination-activating genes). Newborn screening in California established the incidence of severe combined immunodeficiency at 1 in 66,250 live births. The use of hematopoietic stem cell transplantation for PIDs was reviewed, with recommendations to give priority to research oriented to establish the best regimens to improve the safety and efficacy of bone marrow transplantation. These represent only a fraction of significant research done in patients with PIDs that has accelerated the quality of care of these patients. Genetic analysis of patients has demonstrated multiple phenotypic expressions of immune deficiency in patients with nearly identical genotypes, suggesting that additional genetic factors, possibly gene dosage, or environmental factors are responsible for this diversity.
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PMID:Advances in basic and clinical immunology in 2013. 2458 42

A large number of clinically impactful studies and reviews were published in this journal in 2018. This article provides highlights of the original research published in 2018 issues of The Journal of Allergy and Clinical Immunolgy: In Practice on the subjects of anaphylaxis, asthma, dermatitis, drug allergy, eosinophilic disorders, food allergy, immune deficiency, rhinitis, and urticaria/angioedema and mast cell disorders. Within each topic, practical aspects of diagnosis and management are emphasized. Treatments discussed include lifestyle modifications, allergen avoidance therapy, positive and negative effects of pharmacologic therapy, and various forms of immunologic and desensitization management. We hope this review will help readers consolidate and use this extensive and practical knowledge for the benefit of patients.
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PMID:The Journal of Allergy and Clinical Immunology: In Practice 2018 Highlights. 3055 18

Primary atopic disorders describes a series of monogenic diseases that have allergy- or atopic effector-related symptoms as a substantial feature. The underlying pathogenic genetic lesions help illustrate fundamental pathways in atopy, opening up diagnostic and therapeutic options for further study in those patients, but ultimately for common allergic diseases as well. Key pathways affected in these disorders include T cell receptor and B cell receptor signaling, cytokine signaling, skin barrier function, and mast cell function, as well as pathways that have not yet been elucidated. While comorbidities such as classically syndromic presentation or immune deficiency are often present, in some cases allergy alone is the presenting symptom, suggesting that commonly encountered allergic diseases exist on a spectrum of monogenic and complex genetic etiologies that are impacted by environmental risk factors.
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PMID:Primary Atopic Disorders. 3212 83