Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung
| Autor: | Yuhui Xu, K. Frank Austen, Richard A. Flavell, Tatiana Jones, Michael F. Gurish, Joshua A. Boyce, Tong Shi, Jenny Hallgren, Pandelakis A. Koni, J. Pablo Abonia |
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| Rok vydání: | 2006 |
| Předmět: |
Lung Diseases
Male Ovalbumin Integrin alpha4 Immunology Integrin Vascular Cell Adhesion Molecule-1 Inflammation Biology Biochemistry chemistry.chemical_compound Mice Mucoproteins medicine Addressin Animals Mast Cells VCAM-1 Progenitor cell Immunobiology Mice Inbred BALB C Lung Cell adhesion molecule Stem Cells Antibodies Monoclonal Cell Biology Hematology Mast cell medicine.anatomical_structure chemistry biology.protein medicine.symptom Cell Adhesion Molecules |
| Zdroj: | Blood. 108(5) |
| ISSN: | 0006-4971 |
| Popis: | Normal mouse lungs lack appreciable numbers of mast cells (MCs) or MC progenitors (MCp's), yet the appearance of mature MCs in the tracheobronchial epithelial surface is a characteristic of allergic, T-cell-dependent pulmonary inflammation. We hypothesized that pulmonary inflammation would recruit MCp's to inflamed lungs and that this recruitment would be regulated by distinct adhesion pathways. Ovalbumin-sensitized and challenged mice had a greater than 28-fold increase in the number of MCp's in the lungs. In mice lacking endothelial vascular cell adhesion molecule 1 (VCAM-1) and in wild-type mice administered blocking monoclonal antibody (mAb) to VCAM-1 but not to mucosal addressin CAM-1 (MadCAM-1), recruitment of MCp's to the inflamed lung was reduced by greater than 75%. Analysis of the integrin receptors for VCAM-1 showed that in beta7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57BL/6 mice, mAb blocking of alpha4, beta1, or beta7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both alpha4beta1 and alpha4beta7 integrins are essential for the recruitment and expansion of the MCp populations in the lung during antigen-induced pulmonary inflammation. Furthermore, the MCp is currently unique among inflammatory cells in its partial dependence on alpha4beta7 integrins for lung recruitment. |
| Databáze: | OpenAIRE |
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