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)

IgE synthesis results from a complex interaction between T cells, B cells, and allergen presenting cells under the control of T cell and mast cell-/basophil-derived cytokines (IL-4, IL-5, and IL-6). IL-4 provides a first and crucial signal, which does not, however, suffice for the induction of IgE synthesis by human B cells. A second signal is required, which then leads to B cell activation and production of IgE+ B cells. Cognate as well as non-cognate T/B cell interactions or stimulation by Epstein-Barr (EB) virus infection, the ligand for CD40, ACTH, hydrocortisone etc. can provide this signal. Based on this concept of a multicomponent network new approaches may lead to the development of more effective strategies for the treatment of IgE-mediated allergic diseases.
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PMID:[Regulation of IgE synthesis]. 831 Jun 98

Results of studies of the epidemiology, physiology, histopathology, and cell biology of asthma have revised our conception of the disease. Epidemiologic studies have shown asthma to be an important cause of death, suffering, and economic hardship. Physiologic studies have shown that asthma is a chronic illness characterized by persistent bronchial hyperreactivity. Histopathologic studies have shown characteristic changes: epithelial damage, deposition of collagen beneath the basement membrane, eosinophilic and lymphocytic infiltration, and hypertrophy and hyperplasia of goblet cells, submucosal glands, and airway smooth muscle. Studies of the functions of cells in the airway mucosa suggest that asthma may be fundamentally mediated by a difference in the type of lymphocyte predominating in the airway mucosa but may also involve complex interactions among resident and migratory cells. Asthma may thus result from sensitization of a subpopulation of CD4+ lymphocytes, the Th2 subtype, in the airways. These lymphocytes produce a family of cytokines that favor IgE production and the growth and activation of mast cells and eosinophils, arming the airways with the mechanisms of response to subsequent reexposure to the allergen. This conceptual model has stimulated research along lines that will almost certainly lead to powerful new treatments, and it has already put current therapies in a new light, clarifying the role of antinflammatory agents, especially of inhaled corticosteroids. This conceptual model has some limitations: it ignores new evidence on the role of the mast cell in producing cytokines and depends on results of studies of the effects of inhalation of allergen, although most asthma exacerbations are provoked by viral respiratory infection. Preliminary studies suggest that viral infection and allergen inhalation may involve the activation of different pathways, with viral infection activating production of cytokines by airway epithelial cells. Similar study of the mechanisms activated by inhalation of air toxics may provide important clues as to how they might induce or exacerbate asthma.
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PMID:Basic mechanisms of asthma. 854 78

Parainfluenza type 1 (Sendai) virus infection in young rats induces airway growth abnormalities associated with persistent pulmonary dysfunction and hyperresponsiveness. The objectives of this study were to compare virus-susceptible brown Norway (BN) rats and virus-resistant F344 rats and to determine which of several virus-induced structural abnormalities, including bronchiolar hypoplasia, alveolar dysplasia, bronchiolar mural fibrosis, and increases in bronchiolar mast cells, were associated with virus-induced increases in pulmonary resistance and hyperresponsiveness to methacholine. We also determined whether bronchiolar mural thickening and fibrosis may be caused by increased bronchiolar expression of cytokines such as TGF-beta 1 into airways. BN rats infected with virus developed increases in respiratory resistance and hyperresponsiveness that persisted for 28 to 65 d after inoculation. Functional abnormalities were most strongly associated with bronchiolar mural thickening and fibrosis as well as with recruitment of inflammatory cells, including macrophages, mast cells, lymphocytes, and eosinophils, into the bronchiolar wall. F344 rats were resistant to significant virus-induced alterations in bronchiolar airway wall thickness and mast cell increases as well as to pulmonary function abnormalities. BN rats had increase pulmonary mRNA levels of TGF-beta 1 at 10 and 14 d after viral inoculation as compared with F344 rats. BN rats also had greater numbers of bronchiolar macrophages expressing TGF-beta 1 protein that were localized in bronchiolar walls at 10, 14, and 30 d after inoculation. We conclude that recruitment and persistence of airway inflammatory cells and airway wall fibrosis may be important alterations induced by viral lower respiratory disease during early life that can lead to long-term airway dysfunction and hyperresponsiveness. Virus-induced airway fibrosis may be mediated in part by increased TGF-beta 1 gene expression by bronchiolar macrophages in genetically susceptible individuals.
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PMID:Parainfluenza virus-induced persistence of airway inflammation, fibrosis, and dysfunction associated with TGF-beta 1 expression in brown Norway rats. 897 Mar 78

We report here the first demonstration of dengue virus infection and vasoactive cytokine response of a cell of the mast cell/basophil lineage. Infection of KU812 cells was dependent on dengue-specific antibody and gave rise to infectious virions. This antibody-enhanced dengue virus infection triggered a four- to fivefold increase in the release of interleukin-1beta (IL-1beta) and a modest increase for IL-6 but not for an alternate cytokine, granulocyte-macrophage colony-stimulating factor. The results suggest a potential role for mast cells/basophils in the pathogenesis of dengue virus-induced disease.
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PMID:Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a human mast cell/basophil line. 1088 55

Thirty pigs were inoculated with a virulent isolate (Quillota strain) of classical swine fever (hog cholera) virus to establish the chronological occurrence of lesions in the kidney and to determine the mechanism responsible for renal haemorrhages. The study included the use of histopathological, ultrastructural, immunohistochemical (detection of viral antigen gp55, MAC387, lambda chains, CD3 and C1q) and morphometrical techniques (vascular area). Renal interstitial oedema and haemorrhages were detected from 7 days post-inoculation (dpi), associated with a slight interstitial mononuclear infiltrate and evidence of viral infection in macrophages and fibroblasts, and in a small proportion of lymphocytes. Viral infection was not detected in capillary endothelial cells. An intense mononuclear infiltrate, with B cells, T cells and small numbers of macrophages, was detected from 10 dpi. In the final phase of the experiment (14 dpi), slight proliferation and degranulation of mast cells were observed. Increased expression of the C1q component of complement was also detected. A significant increase in vascular area was observed from 7 dpi. These results suggest that haemorrhages observed in the kidneys of pigs inoculated with the Quillota strain resulted from erythrodiapedesis and increased vascular permeability, probably aggravated by mast cell degranulation in the final stage of the experiment. The results suggested that mast cell degranulation was linked to activation of the complement system.
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PMID:Pathogenesis of classical swine fever: renal haemorrhages and erythrodiapedesis. 1090 55

Severe dengue virus infections usually occur in individuals who have preexisting anti-dengue virus antibodies. Mast cells are known to play an important role in host defense against several pathogens, but their role in viral infection has not yet been elucidated. The effects of dengue virus infection on the production of chemokines by human mast cells were examined. Elevated levels of secreted RANTES, MIP-1alpha, and MIP-1beta, but not IL-8 or ENA-78, were observed following infection of KU812 or HMC-1 human mast cell-basophil lines. In some cases a >200-fold increase in RANTES production was observed. Cord blood-derived cultured human mast cells treated with dengue virus in the presence of subneutralizing concentrations of dengue virus-specific antibody also demonstrated significantly (P < 0.05) increased RANTES production, under conditions which did not induce significant degranulation. Chemokine responses were not observed when mast cells were treated with UV-inactivated dengue virus in the presence or absence of human dengue virus-specific antibody. Neither antibody-enhanced dengue virus infection of the highly permissive U937 monocytic cell line nor adenovirus infection of mast cells induced a RANTES, MIP-1alpha, or MIP-1beta response, demonstrating a selective mast cell response to dengue virus. These results suggest a role for mast cells in the initiation of chemokine-dependent host responses to dengue virus infection.
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PMID:Dengue virus selectively induces human mast cell chemokine production. 1213 44

Recent advances in basic and clinical research indicate that interstitial cystitis (IC) is a form of neurogenic inflammation, thereby opening new avenues for research into this painful disease. With this in mind, we have recently developed a rat model of neurogenic inflammation of the bladder produced by a central nervous system viral disease. As in IC, the inflammation in this model develops without direct injury or trauma to the bladder, is non-infectious, and is limited to the bladder. Our most recent studies aimed at further testing the similarity of this animal model to IC by assessing the urine content in histamine with the occurrence of mast cell degranulation in the bladder wall. We further verified for a sex difference in the occurrence of the disease. Our results showed increased levels of urine histamine and mast cell activation during the early stages of the disease. We additionally observed that females had a greater degree of plasma extravasation, while males had a greater cellular infiltration together with worse behavioral signs. Gonadectomy prevented the bladder inflammation altogether in both males and females. These findings further validate our model of neurogenic cystitis to study the neurogenic component of IC.
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PMID:Experimental neurogenic cystitis. 1508 15

Dengue virus is a major mosquito-borne human pathogen with four known serotypes. The presence of antidengue virus antibodies in the serum of individuals prior to dengue virus infection is believed to be an important risk factor for severe dengue virus disease as a result of the phenomenon of antibody-dependent enhancement operating on Fc receptor (FcR)-bearing cells. In addition to blood monocytes, mast cells are susceptible to antibody-enhanced dengue virus infection, producing a number of inflammatory mediators including IL-1, IL-6, and CCL5. Using the human mast cell-like lines KU812 and HMC-1 as well as primary cultures of human cord blood-derived mast cells (CBMC), we aimed to identify the participating FcRs in antibody-enhanced mast cell dengue virus infection, as FcRs represent a potential site for therapeutic intervention. CBMC expressed significant levels of FcgammaRI, FcgammaRII, and FcgammaRIII, and mast cell-like HMC-1 and KU812 cells expressed predominantly FcgammaRII. All four serotypes of dengue virus showed antibody-enhanced binding to KU812 cells. Specific FcgammaRII blockade with mAb IV.3 was found to significantly abrogate dengue virus binding to KU812 cells and CBMC in the presence of dengue-specific antibody. Dengue virus infection and the production of CCL5 by KU812 cells were also inhibited by FcgammaRII blockade.
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PMID:A dominant role for FcgammaRII in antibody-enhanced dengue virus infection of human mast cells and associated CCL5 release. 1694 Mar 32

Mast cells are highly effective sentinel cells, found close to blood vessels and especially common sites of potential infection, such as the skin, airways and gastrointestinal tract. Mast cells participate actively in the innate immune responses to many pathogens through a broad spectrum of mediators that can be selectively generated. They also have a role as innate effector cells in enhancing the earliest processes in the development of acquired immune responses. Studies of bacterial and parasitic models have revealed mast cell dependent regulation of effector cell recruitment, mucosal barrier function and lymph node hypertrophy. An important role for mast cells in viral infection is also implied by several in vivo and in vitro studies. There are multiple direct and indirect pathways by which mast cells can be selectively activated by pathogens including Toll-like receptors, co-receptors and complement component receptors. Understanding the mechanisms and scope of the contribution of mast cells to host defence will be crucial to regulating their activity therapeutically.
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PMID:New and emerging roles for mast cells in host defence. 1712 41

Asthma is a chronic disease characterized by mast cell activation, mucus hypersecretion, airway obstruction, influx and activation of eosinophils, and generation of a predominant T-helper type 2-based cytokine environment. In individuals with established asthma, acute exacerbations requiring hospitalization result primarily from pulmonary viral infection, such as with influenza, rhinovirus, or respiratory syncytial virus. The mechanism for viral exacerbation of the asthmatic response is unclear, but evidence points to a key role for chemokines, a class of cytokines that are important in leukocyte recruitment, inflammatory cell activation, and T-cell differentiation. In this review, we focus on the chemokines upregulated in acute viral-induced exacerbation and examine their role in promoting the virus-induced pathophysiologic response in asthmatic individuals.
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PMID:The role of chemokines in virus-associated asthma exacerbations. 1868 12


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