| 1. |
- Bossios, Apostolos, 1969, et al.
(författare)
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IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; :Nov 26
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Tidskriftsartikel (refereegranskat)abstract
- To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome. Allergy 2009. DOI: 10.1111/j.1398-9995.2009.02271.x.Abstract Background: Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease. Methods: CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed. Results: Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma. Conclusion: CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.
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| 2. |
- O'Neil, Serena, 1981, et al.
(författare)
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Quantitative expression of osteopontin in nasal mucosa of patients with allergic rhinitis: effects of pollen exposure and nasal glucocorticoid treatment
- 2010
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Ingår i: Allergy, Asthma & Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1492. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Osteopontin (OPN) is a multifunctional cytokine that has been primarily investigated in Th1 diseases. Recently, it has also been implicated in Th2-mediated allergic diseases, such as asthma. The expression of OPN in allergic rhinitis (AR) is currently unknown, as is the effect of intranasal glucocorticosteroids (GCs) on that expression. Methods Subjects with AR were randomised to receive treatment with fluticasone propionate (FP) (n = 12) or a placebo (n = 16) over the grass pollen season and nasal biopsies were taken prior to, and during the season. OPN expression in the nasal mucosa was examined with immunohistochemistry. Healthy non-AR controls (n = 5) were used as a comparator. Results OPN expression was detected in epithelial cells, subepithelial infiltrating/inflammatory cells and cells lining the vessels and glands of all subjects. Comparison of the pre- and peak-pollen season biopsy sections in placebo treated patients revealed no increase in OPN expression during the grass pollen season (5.7% vs 6.4%). Treatment with a local glucocorticosteroid did not alter the expression of OPN during pollen exposure (6.2% vs 6.7%). Conclusion OPN has been increasingly associated with the pathogenesis of various Th2-mediated diseases. However, our finding that the OPN expression in the nasal mucosa of AR patients is not significantly affected by allergen exposure and is comparable to that of the healthy controls, suggests that intracellular OPN is not directly involved in the pathogenesis of allergic rhinitis.
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| 3. |
- Samitas, Konstantinos, 1977, et al.
(författare)
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B cells: from early development to regulating allergic diseases.
- 2010
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Ingår i: Archivum immunologiae et therapiae experimentalis. - : Springer Science and Business Media LLC. - 1661-4917 .- 0004-069X. ; 58:3, s. 209-25
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Forskningsöversikt (refereegranskat)abstract
- B lymphocytes are characterized by a unique and highly specialized developmental pathway that is responsible for their vast phenotypic and function diversity. B cell development is strictly regulated to ensure sufficient specific humoral immunity while at the same time avoiding any errors that would compromise B cell functionality. The generation and maintenance of mature B cells from the constant flux of bone marrow progenitors is a complex process that is generally poorly understood, although great progress has been made in recent years. B cells have for long been considered mainly as antibody-producing cells and therefore believed to play an important role in the pathophysiology of allergic diseases, primarily through their ability to produce IgE antibodies. However, recent findings have revealed new aspects of their role in immune responses that place them again under the spotlight as important immune regulators, independent of antibody production. This review focuses on the developmental processes responsible for the numerous phenotypes and functions of the B-lymphocyte pool and the different aspects of effector B cell functionality in the context of allergy.
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| 4. |
- Samitas, Konstantinos, 1977, et al.
(författare)
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Current update on eosinophilic lung diseases and anti-IL-5 treatment
- 2011
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Ingår i: Recent patents on anti-infective drug discovery. - 1574-891X. ; 6:3, s. 189-205
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Forskningsöversikt (refereegranskat)abstract
- Peripheral blood eosinophilia and eosinophilic lung inflammation are common in a variety of pulmonary conditions, including eosinophilic pneumonia and asthma, hypereosinophilic syndrome and Churg-Strauss syndrome. Therapy in most of these clinical entities consists of long-term treatment with systemic corticosteroids, which is not always successful and has substantial side-effects. Interest has increased considerably regarding alternative corticosteroid-sparing "smart" regimens in these diseases that target IL-5, an important regulator of eosinophilic development and function. To date, two humanized monoclonal antibodies, mepolizumab and reslizumab, have been developed that bind to human IL-5. In addition a new monoclonal antibody (MEDI-563) has been recently developed targeting the IL-5 receptor. This review will investigate the current status on IL-5 targeted therapy and related patents regarding eosinophil-driven respiratory diseases, primarily eosinophilic asthma but also CSS and HES. Recent advances and information from clinical trials will be presented in a way that will allow the reader to approach the role of the eosinophil in the lung diseases presented in this review.
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| 5. |
- 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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| 6. |
- 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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