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Asthma, eosinophils, CD34+ progenitor cells

Brittany M A Salter, Steven G Smith, Manali Mukherjee, Sophie Plante, Sakktee Krisna, Graeme Nusca, John Paul Oliveria, Anam Irshad, Gail M Gauvreau, Jamila Chakir, Parameswaran Nair, Roma Sehmi
Activated bronchial epithelial cells (BEC) release various alarmins, including thymic stromal lymphopoietin (TSLP), that drive type 2 inflammation. We hypothesize that BEC-derived factors promote in situ eosinophil differentiation and maturation, a process that is driven by an IL-5-rich microenvironment in asthmatic airways. To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived nonadherent mononuclear cells incubated with BEC supernatants (BECSN) from healthy nonatopic controls (n = 8), mild atopic asthmatics (n = 9), and severe asthmatics (n = 5)...
January 2018: American Journal of Respiratory Cell and Molecular Biology
Z Y Hu, Y M Jia, S J Wang, J Y Han, T Yu
Objective: To investigate the mechanism of CD34(+) progenitor cell differentiation in rat by observing the change relations between the eosinophils (EOS) and the content of Eotaxin and IL-5 in blood and the CD34(+)/CCR3(+), CD34(+)/IL-5Rα+ in bone marrow after occupational asthma (OA) model rats are simulated, and to observe the effect of WTKYD Trraitional Chinese Medicine intervention. Methods: A total of 40 healthy male SD model rats (200~250 g weight) were randomly divided into model contrast Group, prednisone acetate intervention Group, WTKYD+1/2 prednisone acetate intervention Group and WTKYD intervention Group, 10 in each group, and set a Group for blank contrast...
September 20, 2016: Chinese Journal of Industrial Hygiene and Occupational Diseases
Gilda Varricchi, Diego Bagnasco, Matteo Ferrando, Francesca Puggioni, Giovanni Passalacqua, Giorgio W Canonica
Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF...
January 2017: Therapeutic Advances in Respiratory Disease
Xin Feng, Madison K Ramsden, Julie Negri, Mary Grace Baker, Spencer C Payne, Larry Borish, John W Steinke
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) differs from aspirin-tolerant disease in part because of eosinophilic tissue infiltration and overexpression of arachidonic acid metabolic pathway components that lead to enhanced secretion of cysteinyl leukotrienes and prostaglandin (PG) D2 observed constitutively and paradoxically in response to aspirin and other COX inhibitors. We have previously demonstrated the capacity of IFN-γ to drive cysteinyl leukotriene expression and response...
October 2016: Journal of Allergy and Clinical Immunology
Yang-min Jia, Zu-ying Hu, Li Wang, Shu-juan Wang, Jing-yin Han, Ting Yu, Wei-wei Yan
OBJECTIVE: To study the effect of Wenyang Decoction (WD) on the differentiation of CD34+ progenitor cells of occupational asthma (OA) model rats. METHODS: Fifty healthy male SD rats were randomly divided into five groups, i.e., the model group, the blank control group,the WD group,the Western medicine group,the combined group, 10 in each group. Prednisone suspension (10 mg/kg) was administered to rats in the Western medicine group by gastrogavage. WD (20 g/kg) was administered to rats in the WD group by gastrogavage...
January 2016: Chinese Journal of Integrated Traditional and Western Medicine
Steven G Smith, Akash Gugilla, Manali Mukherjee, Kayla Merim, Anam Irshad, Wei Tang, Takashi Kinoshita, Brittany Watson, John-Paul Oliveria, Mike Comeau, Paul M O'Byrne, Gail M Gauvreau, Roma Sehmi
BACKGROUND: Thymic stromal lymphopoietin (TSLP) and IL-33 are considered important initiators of type 2 immunity. In asthmatic patients allergic inflammatory responses are associated with increased lung homing of bone marrow-derived CD34(+) hematopoietic progenitor cells (HPCs), which include eosinophil lineage-committed progenitor cells. In this study we investigated the role of TSLP and IL-33 in the recruitment of progenitor cells to the airways in asthmatic subjects. OBJECTIVES: We sought (i) to examine the effect of allergen inhalation challenge on expression levels of receptors for TSLP (thymic stromal lymphopoietin receptor [TSLPR] and CD127) and IL-33 (ST2) and (ii) investigate the functional effects of these cytokines on HPCs...
June 2015: Journal of Allergy and Clinical Immunology
Yongfu Wu, Hui Fu, Huiling Yang, Hongqiang Wang, Hanbin Zhang, Dongyun Qin
BACKGROUND: The mechanisms regulating airway remodeling changes remain poorly understood. Recently, a smooth muscle progenitor cell was identified in the peripheral circulatory system that plays an important role in the reconstruction of injured blood vessels. However, to the best of our knowledge, there is no report in the medical literature regarding the role of smooth muscle progenitor cells (SPCs) in asthma. OBJECTIVE: The aim of this study was to investigate the relationship between SPCs and the development of airway remodelling in a murine model of asthma...
September 2014: Asian Pacific Journal of Allergy and Immunology
Steven G Smith, Mike Hill, John-Paul Oliveria, Brittany M Watson, Adrian J Baatjes, Benny Dua, Karen Howie, Heather Campbell, Rick M Watson, Roma Sehmi, Gail M Gauvreau
Peroxisome proliferator-activated receptor (PPAR) agonists have been suggested as novel therapeutics for the treatment of inflammatory lung disease, such as allergic asthma. Treatment with PPAR agonists has been shown to inhibit airway eosinophilia in murine models of allergic asthma, which can occur through several mechanisms including attenuated generation of chemoattractants (e.g. eotaxin) and decreased eosinophil migrational responses. In addition, studies report that PPAR agonists can inhibit the differentiation of several cell types...
July 2014: Immunology
H Neighbour, L-P Boulet, C Lemiere, R Sehmi, R Leigh, A R Sousa, J Martin, N Dallow, J Gilbert, A Allen, D Hall, P Nair
BACKGROUND: Several chemokines, notably eotaxin, mediate the recruitment of eosinophils into tissues via the CCR3 receptor. OBJECTIVE: In this study, we investigated the role of CCR3 agonists in asthma by observing the effect of a small molecule antagonist of the CCR3 receptor (GW766994) on sputum eosinophil counts in patients with eosinophilic asthma. METHODS: Clinical and physiological outcomes, the chemotactic activity of sputum supernatant for eosinophils and the presence of eosinophil progenitors in sputum and blood samples were also studied...
April 2014: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
N Punia, S Smith, J V Thomson, A Irshad, P Nair, R Sehmi
BACKGROUND: Lung-homing of progenitor cells is associated with inflammatory and remodelling changes in asthma. Factors that modulate the increased traffic of progenitor cells to the site of inflammation in asthma remain to be defined. Interleukin (IL)-4 and IL-13 are Th2 cytokines that are key regulators of asthma pathology. OBJECTIVE: We investigated the role of IL-4 and IL-13 in modulating the trans-migrational responses of haemopoietic progenitor cells (HPC)...
February 2012: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
H Imaoka, H Campbell, I Babirad, R M Watson, M Mistry, R Sehmi, G M Gauvreau
BACKGROUND: TPI ASM8 contains two modified phosphorothioate antisense oligonucleotides (AON), one targeting the common beta chain (βc) of the IL-3/IL-5/GM-CSF receptors and the other targeting the chemokine receptor CCR3. Inhalation of TPI ASM8 significantly improves lung function and sputum eosinophilia after allergen inhalation challenge in asthmatics. OBJECTIVE: This study assessed whether TPI ASM8 reduces airway levels of haemopoietic progenitor cells. METHODS: This open-label study was conducted in 14 stable, allergic mild asthmatic subjects with early- and late-phase allergen-induced bronchoconstriction...
December 2011: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Thomas Eiwegger, Cezmi A Akdis
IL-33 is becoming a central molecule in allergic asthma that addresses various cascades of innate and adaptive immune responses that lead to inflammation in the lung. Its effects are exerted via its heterodimeric receptor that consists of ST2 and the ubiquitously expressed IL-1 receptor accessory protein (ILRAcP). IL-33 integrates both innate and adaptive immunity in a unique fashion via basophils, mast cells, eosinophils, innate lymphoid cells, NK and NKT cells, nuocytes, Th2 lymphocytes and a CD34(pos) precursor cell population...
June 2011: European Journal of Immunology
Pia Reece, Amudhinie Thanendran, Lynn Crawford, Meri K Tulic, Lehana Thabane, Susan L Prescott, Roma Sehmi, Judah A Denburg
BACKGROUND: Little is known regarding the prenatal determinants of innate immune responses in relation to infant allergic risk. Environmental exposures, including microbial stimuli, might predispose susceptible subjects to atopy and asthma in early infancy or even in utero. OBJECTIVE: Because Toll-like receptors (TLRs) recognize microbial products and because cord blood (CB) progenitor alterations have been observed in neonates at risk for atopy, we investigated the expression and function of TLRs on CB hematopoietic progenitors in relation to atopic risk, as defined by maternal allergic sensitization...
February 2011: Journal of Allergy and Clinical Immunology
Madeleine Rådinger, Apostolos Bossios, Margareta Sjöstrand, You Lu, Carina Malmhäll, Anna-Karin Dahlborn, James J Lee, Jan Lötvall
Emerging evidence suggests that haematopoietic CD34(+) progenitor cells migrate from bone marrow (BM) to sites of allergen exposure where they can undergo further proliferation and final maturation, potentially augmenting the degree of tissue inflammation. In the current study we used a well-characterized mouse model of allergen-induced airway inflammation to determine the role of CCR3 receptor-ligand interactions in the migration and function of CD34(+) cells. Allergen exposure significantly increased BM, blood and airway CD34(+) CCR3(+) cells as well as airway CD34(+) CCR3(+) stem cell antigen-1-positive (Sca-1(+) ) and CD34(+) CD45(+) interleukin-5 receptor-α-positive (IL-5Rα(+) ) cells...
January 2011: Immunology
A Bossios, M Sjöstrand, A-K Dahlborn, K Samitas, C Malmhäll, M Gaga, J Lötvall
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...
July 2010: Allergy
A I Fanat, J V Thomson, K Radford, P Nair, R Sehmi
INTRODUCTION: Human airway smooth muscle (HASM) cells in culture synthesize cytokines and chemokines that may orchestrate the tissue homing and in situ differentiation of haemopoietic progenitor cells from the peripheral circulation. OBJECTIVE: To study the effect of a supernatant from cultured HASM cells on the differentiative and transmigrational responses of haemopoietic progenitor cells. METHODS: HASM cells were grown to confluence and stimulated with a cytomix of TNF-alpha, IL-1beta and IFN-gamma...
July 2009: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Zoulfia Allakhverdi, Michael R Comeau, Dirk E Smith, Dean Toy, Leandra Mfuna Endam, Martin Desrosiers, Yong-Jun Liu, Karen J Howie, Judah A Denburg, Gail M Gauvreau, Guy Delespesse
BACKGROUND: In steady state, hemopoietic progenitors constantly egress from the bone marrow (BM) into the blood and circulate through the peripheral tissues. In allergic diseases, the BM releases increased numbers of CD34(+) progenitor cells that migrate to the site of allergic inflammation, where they differentiate into tissue-dwelling and classic effector cells of allergy, such as mast cells, eosinophils, and basophils. OBJECTIVE: To examine whether peripheral blood CD34(+) cells in addition to being progenitors may also directly function as inflammatory effector cells...
February 2009: Journal of Allergy and Clinical Immunology
Joanna S Makowska, Janina Grzegorczyk, Malgorzata Ciéslak, Barbara Biénkiewicz, Marek L Kowalski
BACKGROUND: Previous studies have suggested that the number of progenitor cells is elevated in the peripheral blood of asthmatic patients and that the number of progenitors correlate with the severity of the disease. OBJECTIVE: To evaluate the number of leukocyte progenitor and eosinophil progenitor cells in the peripheral blood of patients with bronchial asthma in relation to disease severity. METHODS: The study involved 51 patients with asthma (25 patients with a mild form and 26 with a severe form of the disease) and a group of 12 healthy controls...
October 2008: Annals of Allergy, Asthma & Immunology
Hui Mao, Xue Rong Chen, Qun Yi, Su Yun Li, Zeng Li Wang, Fu-Yu Li
The bone marrow eosinophilopoiesis makes a major contribution to the chronic airway inflammation in asthmatic animals and patients. Some anti-asthmatic medicines alleviated the asthmatic airway inflammation by inhibiting the bone marrow eosinophilopoiesis. Immunosuppressive agents have been commonly used in patients with glucocorticoid refractory asthma and have been proved to be effective. However, the research on the effect of the immunosuppressive agents on the bone marrow eosinophilopoiesis has seldom been reported...
July 2008: International Immunopharmacology
Rochelle Fernandes, Merci Kusel, Michael Cyr, Roma Sehmi, Kathryn Holt, Barbara Holt, Tatiana Kebadze, Sebastian L Johnston, Peter Sly, Judah A Denburg, Patrick Holt
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...
May 2008: Pediatric Allergy and Immunology
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