Abstract
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 β7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57BL/6 mice, mAb blocking of α4, β1, or β7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both α4β1 and α4β7 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 α4β7 integrins for lung recruitment.
Original language | English (US) |
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Pages (from-to) | 1588-1594 |
Number of pages | 7 |
Journal | Blood |
Volume | 108 |
Issue number | 5 |
DOIs | |
State | Published - Sep 1 2006 |
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology