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 3-year-old Himalayan cat was diagnosed with concurrent eosinophilic conjunctivitis, herpes virus, and a conjunctival mast cell tumor. Eosinophilic conjunctivitis was verified via cytology from a conjunctival scraping, which revealed 50% eosinophils and 50% neutrophils. Herpes virus was verified via a positive polymerase chain reaction (PCR). Conjunctival scrapings for chlamydia immmunofluorescent antibody (IFA) and herpes IFA were negative. A mycoplasma was detected by a general mycoplasma PCR but the organism did not grow on the available mycoplasma media. The mass was excised and microscopic evaluation revealed a histiocytic mast cell tumor. The mast cell did not recur following local excision (at 1 year follow-up). The eosinophilic conjunctivitis was treated with both topical steroids and systemic megesterol acetate (Ovaban). When topical steroids were used, the herpes virus flared up and resulted in dendritic and geographic corneal ulceration. Therefore, the cat was treated with megesterol acetate and the eosinophilic conjunctivitis was well controlled. Treatment of eosinophilic conjunctivitis in the cat with megesterol acetate may be the treatement of choice due to the possibility of herpes virus.
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PMID:Eosinophilic conjunctivitis, herpes virus and mast cell tumor of the third eyelid in a cat. 1139 7

Mast cells, historically known for their involvement in type I hypersensitivity, also serve critical protective and homeostatic functions. They directly recognize the products of bacterial infection through several surface receptor proteins, releasing proteases, cytokines, and eicosanoid mediators that recruit neutrophils, limit the spread of bacterial infection, and facilitate subsequent tissue repair. In vitro studies suggest that the spectrum of microbes capable of initiating mast cell activation is broad and extends to common respiratory viruses, mycoplasma, and even products of tissue injury, such as nucleotides. TH2-polarized inflammation elicits a reactive hyperplasia of mast cells at the involved mucosal surfaces in both mice and human subject. Several recombinant TH2 cytokines (IL-3, IL-4, IL-5, and IL-9) act synergistically with stem cell factor to facilitate proliferation of nontransformed human mast cells in vitro. IL-4 induces the expression of critical inflammation-associated genes by human mast cells, such as those encoding leukotriene C4 synthase, Fc(epsilon)RI, and several cytokines. Consequently, priming with IL-4 not only amplifies classical Fc(epsilon)RI-dependent mast cell activation but also dramatically alters the product profile of mast cells activated by innate signals and by chemical mediators of inflammation. Strikingly, IL-4 induces an activation response by mast cells to cysteinyl leukotrienes, which act through a receptor shared with uridine diphosphate to induce cytokine generation without exocytosis. It Is possible that alterations in mast cell phenotype by the TH2 milieu of allergy permits otherwise trivial infections or homeostatic chemical signals to initiate harmful inflammatory cascades and sustain tissue pathology. Drug development must take these nonclassical mast cell activation pathways into account without compromising the beneficial and protective functions of mast cells.
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PMID:Mast cells: beyond IgE. 1253 90

Mycoplasma pneumoniae is a respiratory tract pathogen associated with exacerbations in patients with chronic asthma, yet relatively little is known about the potential role of this organism in asthma pathogenesis. Our previous studies demonstrated that RBL-2H3 mast cells co-cultured with M. pneumoniae released preformed inflammatory mediators, synthesized multiple cytokine mRNA species, and released IL-4 protein. In this study, we sought to determine the mechanism by which M. pneumoniae activates mast cell cytokine production. Cytokine mRNA upregulation and IL-4 protein production in RBL cells were induced almost exclusively by plastic-adherent M. pneumoniae cultures (MpA). Organisms grown under non-adherent conditions (MpN) were unable to induce cytokine responses efficiently. Western blots demonstrated that MpA was enriched for P1, the major M. pneumoniae adhesin, compared to MpN. M. pneumoniae-induced IL-4 release from RBL cells was inhibited >85% by anti-P1 monoclonal antibodies. Additionally, a P1-deficient strain of the bacteria was unable to efficiently induce IL-4 release. Desialation of RBL cell surface glycoproteins by neuraminidase treatment eliminated IL-4 release. We conclude that P1 plays an important role in M. pneumoniae-induced cytokine responses in RBL mast cells and that direct contact between the organism and sialated residues on the RBL surface mediates this activation.
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PMID:A role for the Mycoplasma pneumoniae adhesin P1 in interleukin (IL)-4 synthesis and release from rodent mast cells. 1616 2

Mycoplasmas cause chronic inflammation and are implicated in asthma. Mast cells defend against mycoplasma infection and worsen allergic inflammation, which is mediated partly by histamine. To address the hypothesis that mycoplasma provokes histamine release, we exposed mice to Mycoplasma pulmonis, comparing responses in wild-type and mast cell-deficient KitW-sh/KitW-sh (W-sh) mice. Low histamine levels in uninfected W-sh mice confirmed the conventional wisdom that mast cells are principal sources of airway and serum histamine. Although mycoplasma did not release histamine acutely in wild-type airways, levels rose up to 50-fold above baseline 1 week after infection in mice heavily burdened with neutrophils. Surprisingly, histamine levels also rose profoundly in infected W-sh lungs, increasing in parallel with neutrophils and declining with neutrophil depletion. Furthermore, neutrophils from infected airway were highly enriched in histamine compared with naive neutrophils. In vitro, mycoplasma directly stimulated histamine production by naive neutrophils and strongly upregulated mRNA encoding histidine decarboxylase, the rate-limiting enzyme in histamine synthesis. In vivo, treatment with antihistamines pyrilamine or cimetidine decreased lung weight and severity of pneumonia and tracheobronchitis in infected W-sh mice. These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation.
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PMID:Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. 1715 62

Mycoplasma pneumoniae is strongly associated with new onset asthma and asthma exacerbations. Until recently, the molecular mechanisms utilized by M. pneumoniae to influence asthma symptoms were unknown. However, we recently reported that an ADP-ribosylating and vacuolating toxin called the Community Acquired Respiratory Distress Syndrome toxin, CARDS toxin, produced by M. pneumoniae was sufficient to promote allergic inflammation and asthma-like disease in mice. A mouse model of CARDS toxin exposure was used to evaluate total and CARDS-toxin specific serum IgE responses. Mast cell sensitization, challenge, and degranulation studies determined functionality of the CARDS toxin-specific IgE. In the current study, we report that a single mucosal exposure to CARDS toxin was sufficient to increase total serum IgE and CARDS toxin-specific IgE in mice. Mice given a second mucosal challenge of CARDS toxin responded with significant increases in total and CARDS toxin-specific IgE. CARDS toxin-specific IgE bound to an N-terminal peptide of CARDS toxin but not the C-terminal peptide. Likewise, full-length CARDS toxin and the N-terminal peptide induced mast cell degranulation. Altogether, these data demonstrate that exposure to CARDS toxin is sufficient to generate functional IgE in mice. M. pneumoniae and CARDS toxin are strongly associated with asthma exacerbations raising the possibility that the CARDS toxin-specific IgE-mast cell axis contributes to disease pathogenesis.
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PMID:Mycoplasma pneumoniae CARDS toxin elicits a functional IgE response in Balb/c mice. 2819 85

Respiratory viral infections are very important triggers of asthma exacerbation. Recent epidemiologic studies support the hypothesis that they are associated with 80 to 85 % of acute attacks of asthma in children, both in mild exacerbations, and in more severe exacerbations leading to hospital admission. The respiratory syncytial and parainfluenza viruses are predominantly detected in infants, while rhinovirus and mycoplasma are the commonest viruses in children. The detailed mechanism of virus-induced exacerbations remains poorly understood, al though recent studies have provided evidence of increased activation of inflammatory cells in bronchial lavage. Allergic individuals, outside of periods of allergy, do not seem to have more virus-induced respiratory manifestations than nonallergic individuals. In contrast, rhinovirus infection may intensify both the immediate and late response to allergen challenge by increasing mast cell mediator release and recruitment of eosinophils in the lower airways. Human and animal studies suggest that local production of cytokines (IL4, IL8, RANTES, MIP-1a...) and the increased expression of intercellular adhesion molecule 1 (ICAM1) in asthmatic individuals, may play an important role for recruitment and activation of inflammatory cells in the airways. One hypothesis, that remains to be demonstrated, would be that in the presence of Th2 predominance, as occurs in asthma, an excess of IL4 could inhibit the development of cytotoxic CD8, NK and Th1 activity, thereby resulting in decreased IFN production, more severe allergic inflammation and less efficient viral clearance.
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PMID:[Acute viral respiratory tract infections and childhood asthma]. 3228 50