Asthma, eosinophils, CD34+ progenitor cells

Atopy is characterized by eosinophilic inflammation associated with recruitment of eosinophil/basophil (Eo/B) progenitors. We have previously shown that Eo/B progenitor phenotypes are altered in cord blood (CB) in infants at high risk of atopy/asthma, and respond to maternal dietary intervention during pregnancy. As respiratory tract viral infections have been shown to induce wheeze in infancy, we investigated the relationship between CB progenitor function and phenotype and acute respiratory illness (ARI), specifically wheeze and fever...

BACKGROUND: In aspirin-sensitive patients with asthma, bronchial obstruction induced by oral aspirin may be associated with extrabronchial symptoms, suggesting the systemic character of the response. OBJECTIVE: Go assess potential systemic effects of local aspirin challenge, hemopoietic progenitors were measured in the peripheral blood of challenged patients. METHODS: In 19 patients with a history of aspirin-induced asthma, placebo-controlled bronchial challenges with lysine-aspirin were performed...

BACKGROUND: Asthma is characterized by increases in mature eosinophils and their progenitors within the bronchus and bone marrow. IL-5 plays a key role in eosinophil development in the bone marrow and at the site of allergic inflammation. We therefore studied the effects of nebulized IL-5 on eosinophils, their progenitors and in situ haemopoiesis within the airway and bone marrow. METHODS: Nine atopic asthmatics and 10 non-atopic non-asthmatic control volunteers inhaled 10 microg of IL-5 or placebo via a nebulizer in a double-blind, randomized, cross-over study...

Stem cell factor (SCF), the ligand of the c-Kit receptor, is expressed by various structural and inflammatory cells in the airways. Binding of SCF to c-Kit leads to activation of multiple pathways, including phosphatidyl-inositol-3 (PI3)-kinase, phospholipase C (PLC)-gamma, Src kinase, Janus kinase (JAK)/Signal Transducers and Activators of Transcription (STAT) and mitogen activated protein (MAP) kinase pathways. SCF is an important growth factor for mast cells, promoting their generation from CD34+ progenitor cells...

BACKGROUND: Interleukin (IL)-9 is a Th2-derived cytokine with pleiotropic biological effects, which recently has been proposed as a candidate gene for asthma and allergy. We aimed to evaluate the therapeutic effect of a neutralizing anti-IL-9 antibody in a mouse model of airway eosinophilic inflammation and compared any such effect with anti-IL-5 treatment. METHODS: OVA-sensitized Balb/c mice were intraperitoneally pretreated with a single dose (100 microg) of an anti-mouse IL-9 monoclonal antibody (clone D9302C12) or its vehicle...

Eosinophil recruitment to the airways, including involvement of haemopoietic eosinophil-basophil progenitors (Eo/B-CFU), is primarily regulated by interleukin-5 (IL-5) and eotaxin. In this study, we investigated the haemopoietic mechanisms in upper and lower airway eosinophilic inflammation. Ovalbumin (OVA) sensitized and challenged BALB/c mice were used to establish isolated upper (UAC), isolated lower (LAC), or combined upper and lower airway (ULAC) inflammation. Airway, blood and bone marrow responses were evaluated in each model...

BACKGROUND: There is increasing evidence that hemopoietic progenitor cells may traffic from bone marrow to sites of allergen exposure in asthma and undergo in situ differentiation, contributing to ongoing airway inflammation. However, the isolation and detailed phenotyping of true CD34 + progenitors from lung tissue during an allergen-induced airway eosinophilia has not been performed. OBJECTIVE: We attempted to isolate and investigate the in vivo kinetics of hemopoietic progenitor cells and production of eosinophilopoietic mediators in the lung...

BACKGROUND: Eosinophils develop from CD34+ bone marrow progenitors, and evidence increasingly suggests that these progenitors are recruited to the airways in atopic asthmatics after allergen challenge. Moreover, it has been shown that the number of CD34+ progenitors in bronchial tissue correlates with asthma severity. To date, however, little is known about how these cells are recruited into the airways. OBJECTIVE: Our aim was to evaluate the role of 2 chemokines, eotaxin-I and/or eotaxin-2, in the recruitment of newly produced and CD34+ eosinophils to the airways after allergen exposure...

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We investigated the mechanisms by which leukotriene receptor antagonists decrease airway eosinophil number. In a randomized, double-blind crossover study, we examined the effects of 2 weeks of treatment with pranlukast 300 mg twice a day or placebo on allergen-induced changes in airway eosinophil number and bone marrow eosinophil progenitors in 15 subjects with mild asthma. Pranlukast treatment for 2 weeks decreased mean sputum eosinophil count from 0.15 x 10(6)/g (5.3% of cells) before treatment to 0.02 x 10(6)/g (0...

Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells...

There is increasing evidence that primitive progenitors migrate from the bone marrow (BM) via the peripheral circulation to tissue sites where they undergo in situ differentiation to provide a continued source of effector cells, such as eosinophils, during an allergic inflammatory response. To study mechanisms of progenitor cell mobilization in allergic reactions, we investigated fluctuations in the expression of the eotaxin receptor, CC chemokine receptor 3 (CCR3), on CD34+ cells from stable asthmatics following allergen (i...

BACKGROUND: Eosinophils develop from CD34(+) progenitors under the influence of IL-5. Atopic asthmatic individuals have increased numbers of mature eosinophils and eosinophil pro-genitors within their bone marrow and bronchial mucosa. We have previously reported that anti-IL-5 monoclonal antibody treatment decreases total bone marrow and bronchial mucosal eosinophil numbers in asthma. OBJECTIVE: Using an anti-IL-5 monoclonal antibody, we examined the role of IL-5 in eosinophil development within the bone marrow and bronchial mucosa in asthma...

1. Theophylline possesses anti-inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells. 2. Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM-CSF, stem cell factor, IL-3 and IL-5. Apoptosis was measured by flow cytometry of propidium-iodide-stained cells. 3. A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown...

The involvement of chemokines in eosinophil recruitment during inflammation and allergic reactions is well established. However, a functional role for chemokines in eosinophil differentiation has not been investigated. Using in situ RT-PCR, immunostaining, and flow cytometric analysis, we report that human CD34+ cord blood progenitor cells contain CCR3 mRNA and protein. Activation of CD34+ progenitor cells under conditions that promote Th2 type differentiation up-regulated surface expression of the CCR3. In contrast, activation with IL-12 and IFN-gamma resulted in a significant decrease in the expression of CCR3...

1. There are increased numbers of circulating CD34(+) progenitor cells for eosinophils in patients with atopic asthma, with a further increase following allergen exposure or spontaneous worsening of asthma. We investigated the expression of IL-5 and IL-5Ralpha receptor in circulating CD34(+) progenitor cells in allergic asthmatics and the effects of corticosteroids. 2. Using double-staining techniques, up to 50% of CD34(+) cells expressed intracellular IL-5, and by RT - PCR, there was significant expression of IL-5 mRNA...

Asthma is characterized by the accumulation of activated T cells and eosinophils within the airway. Eosinophils derive from CD34(+) bone marrow progenitor cells under the influence of hematopoietic growth factors, subsequently migrating to the airways under the cooperative influence of interleukin (IL)-5 and chemokines, including eotaxin. We compared the relative effects of systemic versus local IL-5 on progenitor-cell mobilization and mature eosinophil phenotype by using flow cytometry, following the administration of intravenous (2 microg) or inhaled (15 microg) IL-5 to nine patients with mild asthma...

The role of inflammatory effector cells in the pathogenesis of airway allergy has been the subject of much investigation. However, whether systemic factors are involved in the development of local responses in both upper and lower airways has not been fully clarified. The present study was performed to investigate aspects of the pathogenesis of isolated allergic rhinitis in a murine model sensitized to ovalbumin (OVA). Both upper- and lower-airway physiological responsiveness and inflammatory changes were assessed, as well as bone marrow progenitor responses, by culture and immunohistological methods...

We and others have shown that IL-5 plays a central role in eosinophil and basophil differentiation, exerting its effects through the IL-5 receptor (IL-5R). Little is currently known concerning regulation of IL-5Ralpha gene transcription in the context of commitment of hemopoietic progenitor cells to the eosinophil and basophil lineages; recent studies have indicated that IL-5 itself can regulate IL-5Ralpha expression on mature eosinophils. We now provide evidence to indicate that IL-5 can upregulate IL-5Ralpha on bone marrow CD34+ progenitors in vitro, as we have demonstrated in vivo in atopic asthmatics...

BACKGROUND: In allergic inflammation and asthma, eosinophils are major effector cells. They have been shown to synthesize at least 23 cytokines, some of which are stored intracellularly in their unique crystalloid granules together with cationic granule protein. Little is known about the synthesis and storage of cytokines relative to cationic granule proteins in maturing eosinophils during eosinophilopoiesis. OBJECTIVE: Our purpose was to analyze the expression of eosinophil-derived mediators, major basic protein (MBP), eosinophil cationic protein (ECP), IL-6, and RANTES, during early stages of eosinophil maturation in CD34(+) cell-derived colonies...