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- Samitas, Konstantinos, 1977, et al.
(författare)
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Osteopontin expression and relation to disease severity in human asthma.
- 2011
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 37:2, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have associated osteopontin (Opn) with allergic inflammation; however, its role in human asthma remains unclear. We measured Opn levels in serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identified cellular sources of Opn and examined possible correlations between Opn expression, disease severity and airway remodeling. Serum samples were obtained from 35 mild-moderate (MMA), 19 severe asthmatics (SA) and 17 healthy controls in steady state and in case of exacerbation. Of these subjects, 29 asthmatics and 9 controls underwent bronchoscopy with endobronchial biopsy and BALF collection. Opn expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane (RBM) thickness and goblet cell hyperplasia were also determined. Serum and BALF Opn levels were significantly increased in all asthmatics in steady state, while serum levels decreased during exacerbations. Opn was upregulated in the bronchial tissue of all patients and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. Opn expression correlated with RBM thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-moderate asthma. Opn expression is upregulated in human asthma, is associated with remodeling changes and its subepithelial expression correlates to disease severity.
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| 2. |
- Samitas, Konstantinos, 1977, et al.
(författare)
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Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.
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