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)

It has been proposed that a specific IgE response contributes to the immunopathology of acute respiratory syncytial virus (RSV) bronchiolitis but previous work has been difficult to replicate. Indirect evidence that might support this contention was sought by measuring total IgE concentrations in bronchoalveolar lavage (BAL) samples obtained from intubated infants and by attempting to detect mRNA for IgE in cells obtained from both the upper and lower respiratory tract. Evidence of significant mast cell activation was sought by measuring tryptase concentrations in BAL fluid and serum. Detectable concentrations of IgE were found in two of seven BAL samples obtained more than five days after intubation and mRNA for IgE was demonstrated in three of six BAL samples and three of six samples obtained from the upper respiratory tract. Tryptase was detectable in 11 of 12 BAL samples with the two highest values detected on day 1. These values were raised compared with control samples but were not such to suggest that mast cell degranulation is the major contributor to the inflammatory process. These results suggest that IgE may be produced in the airways of infants in response to RSV infection. The relationships between IgE production, RSV infection, and symptoms of acute bronchiolitis remain obscure.
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PMID:Tryptase and IgE concentrations in the respiratory tract of infants with acute bronchiolitis. 771 46

Infection of airway epithelial cells with respiratory syncytial virus (RSV) results in the production of a restricted number of cytokines, which may modulate the inflammatory response to infection. To get a better understanding of epithelial cell-mediated inflammatory processes in RSV disease, the aim of the present study was to identify the production of mononuclear cell/eosinophil/mast cell inflammatory chemokines [monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein-1beta, and RANTES] during productive RSV infection in airway epithelial cells. Normal human primary bronchial epithelial cell cultures, nasal epithelial cell explants, and the BEAS-2B airway epithelial cell line were inoculated with RSV, and chemokine induction was assessed during the phase of logarithmic increase in infectious virus production. Only RANTES was found to increase in epithelial cell cultures in an infection-dependent manner. Furthermore, RANTES was released only by RSV-producing cells. To determine whether RANTES was induced by RSV infection in vivo, RANTES was measured in nasal lavage fluids (NLF) from children with RSV-positive and RSV-negative upper respiratory infection and children when they were well. RANTES was increased significantly during RSV infection (128 +/- 38 pg/ml NFL) compared with non-RSV infection (42 +/- 12 pg/ml NFL) and with asymptomatic baseline (13 +/- 4 ng/ml NFL) in the same children. Because RANTES is an effective eosinophil and memory T cell chemoattractant and activator and because eosinophil-dominated inflammation is a hallmark of asthmatic airways, RANTES may play a role in the pathogenesis of RSV-induced exacerbations of airway reactivity and wheezing.
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PMID:RSV infection of human airway epithelial cells causes production of the beta-chemokine RANTES. 912 9

The persistence of wheezing after early wheezing episodes in infancy may be related to the virus involved and to the type of inflammation during the initial wheezing. The role of mast cell activation and leukotriene secretion in wheezing, and the relation to outcome, is not known. Our objective was to study markers of mast cell activation and leukotriene secretion from wheezing infants, and the relation to respiratory syncytial virus (RSV) infection and persistent wheezing. Urinary 9alpha,11beta-PGF(2), a marker of mast cell activation, and urinary leukotriene E4 were measured in 106 infants hospitalized for wheezing during their first year of life. Results were related to the presence of RSV infection and the persistence of wheezing at follow-up 20 months later. Levels of 9alpha,11beta-PGF(2) were higher in infants positive for RSV than in those with RSV negative wheezing, but both groups had higher levels than controls. Leukotriene E4 levels were higher in wheezing infants than in controls. Urinary 9alpha,11beta-PGF(2) levels were higher in infants with transient compared with persistent wheezing. We found a positive correlation between 9alpha,11beta-PGF(2) and leukotriene E4, strongest in infants with RSV negative disease and in infants with persistent wheezing. The results suggest that mast cells play an important role in infant wheezing, and may be a major source of leukotriene secretion in these infants. Mast cell activation and leukotriene secretion were not associated with persistent wheezing.
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PMID:Mast cell activation and leukotriene secretion in wheezing infants. Relation to respiratory syncytial virus and outcome. 1642 53

Respiratory syncytial virus (RSV), a major causative agent of respiratory tract infections, influences allergic diseases. Mast cells, important effector cells in allergic disease, also express chemokine (C-X(3)-C motif) receptor 1 (CX(3)CR1). The RSV attachment glycoprotein (G protein) is structurally similar to CX(3)C ligand 1 (CX(3)CL1), the CX(3)CR1 ligand, suggesting that RSV directly interacts with and affects mast cell function, including degranulation. In this paper, the effect of RSV infection on mast cell function was studied using the human mast cell line (HMC-1). The results showed that RSV infection and replication was inefficient in HMC-1 cells than in human epithelial A549 cells. Additionally, HMC-1 degranulation occurred only in coculture with RSV-infected A549 cells, with up-regulation of TNFalpha secretion. However, direct RSV inoculation and incubation with RSV-infected A549 cell culture medium failed to induce HMC-1 degranulation, suggesting that virus-infected cells are critical for degranulation during RSV infection; however, degranulation does not occur by direct RSV infection into mast cells.
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PMID:Mast cell degranulation is induced by A549 airway epithelial cell infected with respiratory syncytial virus. 1919 74

Human lung fibroblasts (HLFs) treated with the viral mimetic polyinosine-polycytidylic acid (poly I:C) form an extracellular matrix (ECM) enriched in hyaluronan (HA) that avidly binds monocytes and lymphocytes. Mast cells are important innate immune cells in both asthma and acute respiratory infections including respiratory syncytial virus (RSV); however, the effect of RSV on HA dependent mast cell adhesion and/or function is unknown. To determine if RSV infection of HLFs leads to the formation of a HA-enriched ECM that binds and enhances mast cell activity primary HLFs were infected with RSV for 48 h prior to leukocyte binding studies using a fluorescently labeled human mast cell line (LUVA). Parallel HLFs were harvested for characterization of HA production by ELISA and size exclusion chromatography. In separate experiments, HLFs were infected as above for 48 h prior to adding LUVA cells to HLF wells. Co-cultures were incubated for 48 h at which point media and cell pellets were collected for analysis. The role of the hyaladherin tumor necrosis factor-stimulated gene 6 (TSG-6) was also assessed using siRNA knockdown. RSV infection of primary HLFs for 48 h enhanced HA-dependent LUVA binding assessed by quantitative fluorescent microscopy. This coincided with increased HLF HA synthase (HAS) 2 and HAS3 expression and decreased hyaluronidase (HYAL) 2 expression leading to increased HA accumulation in the HLF cell layer and the presence of larger HA fragments. Separately, LUVAs co-cultured with RSV-infected HLFs for 48 h displayed enhanced production of the mast cell proteases, chymase, and tryptase. Pre-treatment with the HA inhibitor 4-methylumbelliferone (4-MU) and neutralizing antibodies to CD44 (HA receptor) decreased mast cell protease expression in co-cultured LUVAs implicating a direct role for HA. TSG-6 expression was increased over the 48-h infection. Inhibition of HLF TSG-6 expression by siRNA knockdown led to decreased LUVA binding suggesting an important role for this hyaladherin for LUVA adhesion in the setting of RSV infection. In summary, RSV infection of HLFs contributes to inflammation via HA-dependent mechanisms that enhance mast cell binding as well as mast cell protease expression via direct interactions with the ECM.
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PMID:Respiratory Syncytial Virus Infection of Human Lung Fibroblasts Induces a Hyaluronan-Enriched Extracellular Matrix That Binds Mast Cells and Enhances Expression of Mast Cell Proteases. 3204 99