Modulation of beta1-integrins on hemopoietic progenitor cells after allergen challenge in asthmatic subjects.
J Allergy Clin Immunol
; 122(4): 803-810, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-18760454
ABSTRACT
BACKGROUND:
Mobilization of hemopoietic progenitor cells from the bone marrow (BM) is a feature of inflammatory asthmatic responses. Understanding the mechanisms regulating progenitor cell mobilization and trafficking to the peripheral circulation might be important for the development of effective asthma therapies.OBJECTIVE:
We investigated the role of adhesion molecules in the mobilization of hemopoietic progenitor cells from the BM during an allergen-induced asthmatic response.METHODS:
BM and peripheral blood samples were obtained from dual-responders with mild asthma before and at several time points after allergen challenge. Fluctuations in expression and adhesive properties of beta1- and beta2-integrins on CD34(+)CD45(+) progenitor cells were assessed by using flow cytometry and adhesion to protein-coated wells, respectively.RESULTS:
On BM-derived CD34(+)CD45(+) cells, expression of very late antigen (VLA) 4, but not VLA-5 or Mac-1, decreased significantly 24 hours after allergen challenge and had begun to recover by 48 hours after challenge. In peripheral blood allergen challenge induced a significant decrease in VLA-4 levels after 6 hours, which had not recovered by 96 hours after challenge. Similarly, VLA-5 expression decreased, most prominently at 72 to 96 hours after allergen challenge. In contrast, Mac-1 levels did not change. Chemokine-stimulated adhesion of BM-derived CD34(+)CD45(+) cells to fibronectin was significantly attenuated 24 hours after challenge. Furthermore, adhesion to fibronectin and vascular cell adhesion molecule 1 was greatly reduced by anti-VLA-4 or anti-VLA-5 antibodies.CONCLUSIONS:
Preferential downregulation of beta1-integrin expression on progenitor cells can reduce the tethering forces to BM components, thus facilitating their egress to the peripheral circulation during an allergic inflammatory response.
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Base de dados:
MEDLINE
Assunto principal:
Asma
/
Células-Tronco Hematopoéticas
/
Alérgenos
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Regulação da Expressão Gênica
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Integrina beta1
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article