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Human Lung Mast Cells (human + lung_mast_cell)
Selected AbstractsMast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6ALLERGY, Issue 8 2010P.-O. Girodet To cite this article: Girodet P-O, Ozier A, Trian T, Begueret H, Ousova O, Vernejoux J-M, Chanez P, Marthan R, Berger P, Tunon de Lara JM. Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6. Allergy 2010; 65: 1004,1012. Abstract Background:, Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion. Methods:, Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell,BSM interaction was assessed using 3H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry. Results:, Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. Such an adhesion was increased in normal BSM cells under inflammatory condition, whereas it was maximal in asthmatic BSM cells. Blockade of either CD51 or CD44 significantly decreased mast cell adhesion to BSM. At the molecular level, protein and the transcriptional expression of type I collagen, CD51 or CD44 remained unchanged in asthmatic BSM cells or in mast cells/BSM cells under inflammatory conditions, whereas that of CD44 variant isoform 6 (v6) was increased. Conclusions:, Mast cell,BSM cell adhesion involved collagen, CD44, and CD51, particularly under inflammatory conditions. CD44v6 expression is increased in asthmatic BSM cells. [source] Angiogenesis and lymphangiogenesis in bronchial asthmaALLERGY, Issue 8 2010A. Detoraki To cite this article: Detoraki A, Granata F, Staibano S, Rossi FW, Marone G, Genovese A. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy 2010; 65: 946,958. Abstract Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders. [source] The long-acting ,-adrenoceptor agonist, indacaterol, inhibits IgE-dependent responses of human lung mast cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009Anne-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] Desensitisation of mast cell ,2 -adrenoceptor-mediated responses by salmeterol and formoterolBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2004Anne-Marie Scola The long-acting ,2 -adrenoceptor agonist formoterol (10,10,10,6M) inhibited the IgE-dependent release of histamine from human lung mast cells in a concentration-dependent manner. Formoterol was more potent and a full agonist relative to the nonselective , -adrenoceptor agonist isoprenaline. By contrast, the long-acting ,2 -adrenoceptor agonist salmeterol (10,10,10,6M) was about two-thirds less efficacious than either formoterol or isoprenaline as an inhibitor of histamine release. Isoprenaline, formoterol and salmeterol (all at 10,5M) increased total cell cAMP levels in mast cells over basal by 361±90 (P<0.05), 321±89 (P<0.05) and 64±24% (P>0.05), respectively. Long-term (24 h) incubation of mast cells with formoterol (10,6M) or salmeterol (10,6M) essentially abolished the subsequent ability of isoprenaline to inhibit histamine release. Both formoterol and salmeterol were more effective at inducing the functional desensitisation than isoprenaline (10,6M) or the short-acting ,2 -adrenoceptor agonist salbutamol (10,6M). The desensitisation induced by long-term treatments with salmeterol and formoterol was specific for ,2 -adrenoceptor-mediated inhibition of histamine release as the inhibitory effects of alternative cAMP-elevating compounds, prostaglandin E2, a receptor-mediated activator of adenylate cyclase, and forskolin, a direct activator of adenylate cyclase, were unaffected by desensitising treatments. Radioligand binding studies were performed to determine ,2 -adrenoceptor density in cell membranes after pretreatment (24 h) of cells with agonists. Isoprenaline, formoterol and salmeterol (all at 10,6M) reduced ,2 -adrenoceptor density by 13±5 (P>0.05), 49±13 (P<0.05) and 35±17% (P>0.05), respectively. These data indicate that long-term exposure of mast cells to both salmeterol and formoterol can cause substantial levels of desensitisation to ,2 -adrenoceptor-mediated responses in mast cells. British Journal of Pharmacology (2004) 141, 163,171. doi:10.1038/sj.bjp.0705599 [source] Airway smooth muscle proliferation and survival is not modulated by mast cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2010D. Kaur Summary Background Airway smooth muscle (ASM) hyperplasia and mast cell localization within the ASM bundle are important features of asthma. The cause of this increased ASM mass is uncertain and whether it is a consequence of ASM,mast cell interactions is unknown. Objective We sought to investigate ASM proliferation and survival in asthma and the effects of co-culture with mast cells. Methods Primary ASM cultures were derived from 11 subjects with asthma and 12 non-asthmatic controls. ASM cells were cultured for up to 10 days in the presence or absence of serum either alone or in co-culture with the human mast cell line-1, unstimulated human lung mast cells (HLMC) or IgE/anti-IgE-activated HLMC. Proliferation was assessed by cell counts, CFSE assay and thymidine incorporation. Apoptosis and necrosis were analysed by Annexin V/propidium iodide staining using flow cytometry and by assessment of nuclear morphology using immunofluorescence. Mast cell activation was confirmed by the measurement of histamine release. Results Using a number of techniques, we found that ASM proliferation and survival was not significantly different between cells derived from subjects with or without asthma. Co-culture with mast cells did not affect the rate of proliferation or survival of ASM cells. Conclusion Our findings do not support a role for increased airway smooth proliferation and survival as the major mechanism driving ASM hyperplasia in asthma. Cite this as: D. Kaur, F. Hollins, R. Saunders, L. Woodman, A. Sutcliffe, G. Cruse, P. Bradding and C. Brightling, Clinical & Experimental Allergy, 2010 (40) 279, 288. [source] | ||||||||||