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Mast Cell Responses (mast + cell_response)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008
Akiko Nagasaka
Abstract Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and Fc,RI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN,/,) and -sufficient (OPN+/+) mice without significant differences in yield, purity, granularity, and viability. Using OPN,/, FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin,,v). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN,/, mice compared with OPN+/+ mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions. See accompanying commentary at http://dx.doi.org/10.1002/eji200738131 [source]

Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis

HEPATOLOGY, Issue 2 2001
Monica G. Chiaramonte
In several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity and mortality. Here, using a model of infection-induced liver fibrosis, we show that interleukin (IL)-13 is required at all stages of Schistosomiasis mansoni infection to induce fibrosis. IL-4 production was preserved in IL-13,deficient mice, yet failed to significantly contribute to the fibrotic response in either acute or chronic infection. Significant fibrosis develops in all infected mice, although the magnitude of the response varies widely in inbred mice. C3H/HeN, BALB/c, and C57BL/6 mice develop high, intermediate, and low levels of fibrosis, respectively. Despite these differences, IL-13 antagonism resulted in a marked amelioration of fibrosis in all strains. The fibrotic mechanism in the high- and low-responder strains was unrelated to their tissue eosinophil or mast cell responses, but did correlate with their patterns of IL-13, IL-10, and interferon gamma (IFN-,) mRNA expression. Indeed, severe fibrosis correlated with a high IL-13 and low IFN-,/IL-10 mRNA response. Because fibrotic diseases are typically progressive disorders, an important issue was to determine whether IL-13 inactivation might be used to treat an established and ongoing fibrotic disease. Here, IL-13 antagonism was highly efficacious, even after fibrosis and the Th2 cytokine response were firmly established. These studies demonstrate the central role played by IL-13 in fibrogenesis and suggest that therapeutic approaches aimed at disrupting the IL-13 pathway will be highly effective at preventing fibrotic disease caused by chronic Th2-mediated inflammatory reactions. [source]

The long-acting ,-adrenoceptor agonist, indacaterol, inhibits IgE-dependent responses of human lung mast cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009
Anne-Marie Scola
Background and purpose:, The long-acting ,2 -adrenoceptor agonist, indacaterol, has been developed as a bronchodilator for the therapeutic management of respiratory diseases. The aim of the present study was to determine whether indacaterol has any anti-inflammatory activity. To this end, the effects of indacaterol on human lung mast cell responses were investigated. Experimental approach:, The effects of indacaterol, and the alternative long-acting ,-agonists formoterol and salmeterol, were investigated on the IgE-dependent release and generation of histamine, cysteinyl-leukotrienes and prostaglandin D2 from human lung mast cells. Moreover, the extent to which long-term (24,72 h) incubation of mast cells with long-acting ,-agonists impaired the subsequent ability of ,-agonists to inhibit mast cell responses was assessed. Key results:, Indacaterol was as potent and as efficacious as the full agonist, isoprenaline (EC50, ,4 nmol·L,1), at inhibiting the IgE-dependent release of histamine from mast cells. Formoterol was a full agonist whereas salmeterol was a partial agonist as inhibitors of histamine release. All three long-acting ,-agonists were effective inhibitors of the IgE-dependent generation of cysteinyl-leukotrienes and prostaglandin D2. Long-term incubation of mast cells with long-acting ,-agonists led to a reduction in the subsequent ability of ,-agonists to stabilize mast cell responses. This tendency to induce functional desensitization was least evident for indacaterol. Conclusions and implications:, Indacaterol is an effective inhibitor of the release of mediators from human lung mast cells. This suggests that, as well as bronchodilation, mast cell stabilization may constitute an additional therapeutic benefit of indacaterol. [source]