| 1. |
- Custovic, A., et al.
(author)
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EAACI position statement on asthma exacerbations and severe asthma
- 2013
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In: Allergy. - : Wiley. - 0105-4538. ; 68:12, s. 1520-1531
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Journal article (peer-reviewed)abstract
- Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.
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| 2. |
- Diamant, Zuzana, et al.
(author)
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Toward clinically applicable biomarkers for asthma : An EAACI position paper
- 2019
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:10, s. 1835-1851
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Journal article (peer-reviewed)abstract
- Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
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| 3. |
- Eger, Katrien, et al.
(author)
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The effect of the COVID-19 pandemic on severe asthma care in Europe : will care change for good?
- 2022
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In: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:2
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Journal article (peer-reviewed)abstract
- Background The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.
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| 4. |
- Johansson, Anna-Karin, 1974, et al.
(author)
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Allergen-induced traffic of bone marrow eosinophils, neutrophils and lymphocytes to airways
- 2004
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In: Eur J Immunol. ; 34:11
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Journal article (peer-reviewed)abstract
- We evaluated whether bone marrow (BM) inflammatory cells have capacity to traffic into the airways following allergen exposure in a mouse model of allergen-induced airway inflammation. We also evaluated the effect of IL-5 overexpression on (i) the production of eosinophils in BM, (ii) the accumulation of eosinophils, neutrophils and lymphocytes in blood and airways and (iii) the changes in CD34(+) cell numbers in BM, blood and airways. Bromodeoxyuridine (BrdU) was used to label cells produced during the exposure period. Furthermore, CD3 splenocytes were adoptively transferred to investigate the BM inflammatory response. Allergen exposure induced traffic of BM eosinophils, neutrophils and lymphocytes to the airways and increased the number of BrdU(+) eosinophils, neutrophils, lymphocytes and CD34(+) cells in BALf. IL-5 overexpression enhanced the eosinophilopoiesis and increased the presence of BrdU(+) eosinophils and CD34(+) cells in airways and enhanced the number of CD34(+) cells in BM and blood after allergen exposure. Adoptive transfer of CD3 lymphocytes overexpressing IL-5 caused increased BM eosinophilia. In conclusion, allergen exposure induces traffic of not only newly produced eosinophils but also newly produced neutrophils and lymphocytes into the airways.
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| 5. |
- Papadopoulos, Nikolaos G, et al.
(author)
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Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Journal article (peer-reviewed)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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| 6. |
- Rådinger, Madeleine, 1967, et al.
(author)
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Regulatory role of CD8+ T lymphocytes in bone marrow eosinophilopoiesis
- 2006
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In: Respir Res. - : Springer Science and Business Media LLC. - 1465-993X. ; 7
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Journal article (peer-reviewed)abstract
- BACKGROUND: There is a growing body of evidence to suggest that CD8+ T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8+ T lymphocytes, as well as CD4+ T lymphocytes, may be involved in this process. METHODS: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3+ T lymphocytes (NJ.1638; CD3IL-5+ mice) were bred with gene knockout mice lacking either CD4+ T lymphocytes (CD4-/-) or CD8+ T lymphocytes (CD8-/-) to produce CD3IL-5+ knockout mice deficient in CD4+ T lymphocytes (CD3IL-5+/CD4-/-) and CD8+ T lymphocytes (CD3IL-5+/CD8-/-), respectively. Secondly, CD3+, CD4+ and CD8+ T lymphocytes from naive CD3IL-5+ and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3IL-5+, CD3IL-5+/CD8-/- and CD3IL-5+/CD4-/- mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments. RESULTS: The number of BM eosinophils was significantly reduced in CD3IL-5+/CD8-/- mice compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice. Serum IL-5 was significantly higher in CD3IL-5+/CD4-/- mice compared to CD3IL-5+ mice but there was no difference in serum IL-5 between CD3IL-5+/CD4-/- and CD3IL-5+/CD8-/- mice. Adoptive transfer of CD8+, but not CD4+ T lymphocytes from naive CD3IL-5+ and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3IL-5+/CD8-/- mice developed lower numbers of BM eosinophils compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice. CONCLUSION: This study shows that CD8+ T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice.
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| 7. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways in vivo
- 2004
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In: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 117:2, s. 149-54
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Journal article (peer-reviewed)abstract
- Currently, there is no effective pharmacotherapy against exaggerated mobilisation of neutrophils in human airway diseases such as chronic obstructive pulmonary disease and asthma. We evaluated the effect of two synthetic vasoactive intestinal peptide (VIP)-like analogues on cytokine-induced neutrophil recruitment in airways in vivo. Recombinant interleukin (IL)-1 beta was administered intratracheally (i.t.) to intubated, spontaneously breathing Sprague-Dawley rats. The rats were pretreated either with a VIP synthetic peptide analogue, a pituitary adenylate cyclase-activating peptide (PACAP)-1-27 synthetic analogue, the beta(2)-adrenoceptor agonist salbutamol or vehicle, systemically or locally. Differential cell counts were performed on bronchoalveolar lavage fluid (BALf) cytospins. Effects on mean arterial blood pressure (MAP) were monitored in separate experiments. Systemic administration of the VIP analogue, the PACAP analogue and salbutamol attenuated the cytokine-induced increase in BALf neutrophil number. Local administration of the VIP analogue and salbutamol, but not the PACAP analogue, also decreased the neutrophil number in BALf. Local administration of the VIP analogue and salbutamol caused a transient decrease in MAP. Systemic or local administration of a synthetic VIP peptide analogue inhibits cytokine-induced neutrophil recruitment in airways in vivo. This action is exerted without severe, sustained cardiovascular side effects, and deserves to be further evaluated in obstructive pulmonary diseases in human.
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| 8. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Allergen exposure-induced differences in CD34+ cell phenotype: relationship to eosinophilopoietic responses in different compartments
- 2004
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In: Blood. ; 103:4, s. 1270-7
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Journal article (peer-reviewed)abstract
- We hypothesized that the allergen-induced increased number of airway eosinophils results from increased recruitment of eosinophils from bone marrow (BM) and local development of CD34(+) cells into eosinophils. We also assumed that the phenotype of airway eosinophils depends on whether these cells have differentiated within BM or airway. C57BL/6 mice were sensitized and subsequently exposed to ovalbumin (OVA) on 5 consecutive days. Newly produced cells were labeled with a thymidine analog. Clonogenic activity and interleukin 5 (IL-5) release from bronchoalveolar lavage fluid (BALf) CD34(+) cells were evaluated by using cell-culture techniques. Allergen exposure induces increase in CD135(+) primitive myeloid progenitors within the BM CD34(+) cell population, without significant changes in total number of CD34(+) cells or newly produced CD34(+) cells. CD34(+)/IL-5Ralpha(+) cells in the first stage of cell differentiation were found only in BM, arguing that early commitment of CD34(+) cells into the eosinophil lineage is restricted to the BM compartment. Allergen exposure induces a shift in differentiation of BM, blood, and BALf eosinophillineage-committed CD34(+) cells toward mature eosinophils and recruitment of these cells via blood into airway. We further demonstrate in vitro that ability to multiply persists in BALf CD34(+) cells but not CD34(-) cells, likely via autocrine IL-5 release and IL-5-induced up-regulation of IL-5Ralpha.
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| 9. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Impact of IL-17 on cells of the monocyte lineage in health and disease.
- 2009
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In: Endocrine, metabolic & immune disorders drug targets. - 1871-5303. ; 9:2, s. 178-86
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Journal article (peer-reviewed)abstract
- Discovered in 1993, IL-17 has been the focus of intensive research during the last decade, in particular because of its neutrophil-accumulating capacity in several mammalian organs. We now know that the IL-17 family includes as a minimum 6 members, of whom at least IL-17A and IL-17F can be produced by T cells. Thus, IL-17 is positioned at the interface of acquired and innate immunity and constitutes a link between T cell activity and the accumulation of neutrophils locally in organs. Interestingly, there is now accumulating evidence that IL-17 has effects on myeloid cells other than neutrophils as well, namely on cells of the monocyte lineage. This review article scrutinizes the evidence that IL-17 exerts a functional impact on the cytokine production and functional activity in cells of the monocyte lineage in health and disease. Notably, this evidence includes data suggesting that there are conditions in which cells of the monocyte lineage are likely to play a significant pathogenic role and where IL-17 is directly controlling the activity of these key effector cells.
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| 10. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Increased number of CD34+ cells in nasal mucosa of allergic rhinitis patients: inhibition by a local corticosteroid.
- 2005
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In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894. ; 35:1, s. 34-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood. OBJECTIVE: We aimed to evaluate how allergen exposure affects the number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR) patients and whether any such effect is influenced by local corticosteroid treatment. Also, we evaluated changes in the number of CXC receptor 4-positive cells (CXCR4+), since the CXCR4 ligand (stromal cell-derived factor-1 (SDF-1)) is a potent chemoattractant for haematopoietic progenitors. METHODS: In a double-blind, randomized study, pollen-sensitized AR patients were treated with a nasal corticosteroid fluticasone propionate (FP, 200 microg/day) or placebo throughout the pollen season. Nasal biopsies were taken before and during the season. CD34 and CXCR4 were stained using immunohistochemistry. RESULTS: The pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in placebo-treated patients, but not in FP-treated patients. The mean pollen season-induced increase in CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in FP-treated patients was lower compared with placebo-treated patients. CONCLUSION: A pollen season increases the number of CD34+ cells in nasal tissue accompanied by an increase in the number of CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils in subjects with AR. Treatment with a local corticosteroid provides protection against this pollen-induced increase in tissue CD34+ cells and CD34+ eosinophils possibly via inhibition of allergen-induced CXCR4-mediated recruitment of CD34+ haematopoietic progenitors into airways and their further differentiation into eosinophils within the tissue.
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| 11. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation
- 2005
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In: American journal of respiratory cell and molecular biology. - 1044-1549. ; 33:3, s. 248-53
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Journal article (peer-reviewed)abstract
- Recent data indicate that the proinflammatory cytokine, interleukin (IL)-17, stimulates certain effector functions of human macrophages. We evaluated whether IL-17 mediates allergen-induced accumulation of airway macrophages and, if so, whether such an effect relates to the control of macrophage recruitment and survival. BALB/c mice were sensitized and challenged with ovalbumin. Three hours before challenge an anti-mouse IL-17 mAb (a-IL-17) was administered. Sampling was conducted 24 h after the allergen challenge. In vitro chemotaxis assay for blood monocytes and culture of airway macrophages, immunocytochemistry for Fas-antigen, and matrix metalloproteinase-9 (MMP-9) were used to determine the effect of IL-17 on the recruitment, survival, and activity of airway macrophages. A-IL-17 reduced the number of airway neutrophils and macrophages after allergen challenge. In vitro, recombinant IL-17 induced migration of blood monocytes and prolonged survival of airway macrophages. A-IL-17 also increased the expression of Fas-antigen in airway macrophages in vivo. Finally, the expression of MMP-9 by airway neutrophils and macrophages in vivo was downregulated by a-IL-17. This study indicates that endogenous IL-17 mediates the accumulation of macrophages during allergen-induced airway inflammation. IL-17 exerts its effects by acting directly on airway macrophages by promoting their recruitment and survival. Furthermore, IL-17 is involved in controlling the proteolytic activity of macrophages and neutrophils in allergen-induced airway inflammation.
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| 12. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Intranasal fluticasone propionate inhibits allergen induced bone marrow eosinophilia in mice.
- 2002
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In: Pulmonary pharmacology & therapeutics. - : Elsevier BV. - 1094-5539. ; 15:2, s. 129-34
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Journal article (peer-reviewed)abstract
- Local corticosteroids are currently the most efficient safe anti-allergic treatment, which attenuate eosinophilic tissue inflammation through several mechanisms. We evaluated the effect of local airways corticosteroid on repeated allergen exposure-induced bone marrow activation and airway eosinophilia using the number of eosinophils in bone marrow, bronchoalveolar lavage fluid (BALf) and airways tissue as study end-points. Male BALB/c mice were sensitized by intraperitoneal injections of aluminum-precipitated ovalbumin (OVA) on two different days (5 days apart). Eight days after the second sensitization, the animals were challenged intranasally with OVA or phosphate-buffered saline (PBS) on 5 consecutive days. Concomitantly with challenges mice were treated with fluticasone propionate or respective vehicle. OVA exposures induced a significant increase in eosinophil numbers in bone marrow, BALf and airways tissue (P<0.005). Treatment with fluticasone propionate significantly reduced the increase of absolute number of mature bone marrow eosinophils (P=0.014) and showed a tendency towards decrease in the immature bone marrow eosinophil number (P=0.057) compared to controls. However, fluticasone propionate had no significant effect on BALf and airways tissue eosinophils (P=0.28 and 0.07, respectively). In this murine allergy model intranasal corticosteroid reduced number of bone marrow mature eosinophils, but did not significantly affect airways cell populations.
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| 13. |
- Sergejeva, Svetlana, 1972
(author)
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Mechanisms of allergic airway inflammation. Role of bone marrow
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Allergic airway (AW) inflammation is characterized by accumulation of inflammatory cells within the AW. It is likely that the accumulation of cells within AW is a combination of increased production, migration and prolonged survival of the cells. Inflammatory cells develop from CD34+hematopoietic progenitor cells. Importantly, allergic subjects have increased numbers of CD34+progenitors in bone marrow (BM) and AW. The aims of this thesis were to determine the mechanisms underlining the allergeninduced accumulation of eosinophils and neutrophils in the AW. With reference to allergen-induced AW eosinophilia, the contribution of eosinophilopoiesis in different compartments was studied. In addition, the contribution of the pro-inflammatory cytokine IL-17 in accumulation of eosinophils and neutrophils within the AW was evaluated. The effect of local corticosteroids and systemic blockage of IL-17 cytokine, respectively, were determined. For that purpose, mice models of allergen exposure-induced allergic inflammation and nasal biopsies from allergic rhinitis patients were used. Repeated allergen exposure of sensitized mice resulted in an increase in the number of primitive myeloid progenitors within the BM CD34+cell population. The earliest eosinophil-committed CD34+cells were restricted to the BM compartment. After the allergen exposure, a substantial part of CD34+progenitor cells was de novo produced. In the BM, allergen exposure increased the number of CD34+eosinophilic cells and CD34-mature eosinophils. In blood and AW, allergen exposure induced an increase in the number of CD34+eosinophilic cells, CD34- mature eosinophils and also in newly produced CD34+cells. Furthermore, allergen exposure induced a shift in differentiation of BM, blood and BALf eosinophil-committed CD34+cells towards more mature eosinophils. Importantly, AW CD34+cells from allergen-exposed mice expressed stem cell antigen (Sca-1), produced eosinophil colonies and in response to stimulation with IL-5 expressed IL-5 receptor a chain (IL-5Ra). Moreover, AW CD34+eosinophilic cells themselves released high amounts of IL-5 after unspecific stimulation. In the mouse model of repeated allergen exposure, administration of an intranasal corticosteroid, fluticasone propionate (FP), significantly reduced the allergen-induced elevation of BM eosinophil number, without substantial effect on the number of AW eosinophils. In subjects with allergic rhinitis, the exposure to allergen increased the number of nasal mucosal CD34+hematopoietic cells concomitantly with up-regulation of CXCR4 expression within the CD34+cell population. Furthermore, also the number of CD34+eosinophils in nasal mucosa was increased following exposure to allergen. A local corticosteroid, FP, provided protection against this pollen-induced increase in tissue CD34+cells. The systemic pre-treatment with an anti-IL-17 antibody in allergen-exposed mice reduced the number of AW neutrophils, but not eosinophils, without any significant changes in BM granulocyte counts. In addition, the expression of matrix metalloproteinase-9 (MMP-9) by AW neutrophils but not eosinophils was downregulated by the pre-treatment with anti-IL-17 antibody. In conclusion, this thesis demonstrates the exclusive role of BM in the first-line commitment of hematopoietic progenitors into the eosinophilic lineage. Importantly, allergen exposure induces not only a shift in the differentiation of eosinophil-committed progenitors towards mature cells, but also increases in the number of primitive myeloid progenitors in BM. In response to allergen exposure, CD34+progenitor cells are mobilized into the airways with one mechanism being CXCR4-mediated cell recruitment. The AW CD34+cells maintain a phenotype of a true hematopoietic progenitor cells and retain the ability to multiply likely via autocrine IL-5 release and IL-5-induced up-regulation of IL-5Ra. Local corticosteroids inhibit the allergen-induced BM and AW eosinophilopoiesis as well as allergen-induced CXCR4-mediated recruitment of CD34+cells into AW. Endogenous IL-17 increases the number of MMP-9+ neutrophils in allergic AW inflammation, without substantial effect on the number of eosinophils.
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| 14. |
- Sitkauskiene, Brigita, et al.
(author)
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Regulation of Bone Marrow and Airway CD34+ Eosinophils by Interleukin-5
- 2004
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In: Am J Respir Cell Mol Biol. ; 30:3
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate the effect of a neutralizing anti-interleukin (IL)-5 monoclonal antibody (TRFK-5) on bone marrow and airway CD34(+) and immature eosinophils. A focus was to determine the effect of the timing of treatment. Balb/c mice were ovalbumin-sensitized and subsequently exposed to ovalbumin for 5-10 d via airway route. Animals were treated intraperitoneally with TRFK-5 or its isotype control (50 microg) once at different time points. Newly produced eosinophils were labeled using 5-bromo-2'-deoxyuridine (BrdU). BrdU(+) and CD34(+) eosinophil numbers were examined by immunocytochemistry. TRFK-5 reduced bone marrow immature eosinophils within 3 d. This effect was closely related to a reduction of BrdU(+) and CD34(+) bone marrow eosinophils, and reduced numbers of blood eosinophils. However, bronchoalveolar lavage (BAL) eosinophilia was not attenuated to the same degree. The effect of TRFK-5 was most prominent in the extended allergen-exposure protocol, where the treatment was given in the middle of the exposure, with strongly reduced bone marrow CD34(+) and immature bone marrow eosinophils, blood eosinophils as well as BAL BrdU(+) eosinophils, and BAL CD34(+) eosinophils. These data argue that anti-IL-5 downregulates eosinophilopoiesis within 3 d by action in the bone marrow, by inhibition of the early stages of eosinophil maturation from CD34(+) cells.
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