Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung

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.

Hallgren, JennyHarvard Medical School, Boston, MA(Swepub:uu)jehal516 (författare)
Jones, Tatiana (författare)
Shi, Tong (författare)
Xu, Yuhui (författare)
Koni, Pandelakis (författare)
Flavell, Richard A (författare)
Boyce, Joshua A (författare)
Austen, K Frank (författare)
Gurish, Michael F (författare)
Harvard Medical School, Boston, MA (creator_code:org_t)

Ingår i:Blood: American Society of Hematology108:5, s. 1588-15940006-49711528-0020

Av författaren/redakt...: Abonia, J Pablo; Hallgren, Jenny; Jones, Tatiana; Shi, Tong; Xu, Yuhui; Koni, Pandelakis; visa fler...; Flavell, Richard ...; Boyce, Joshua A; Austen, K Frank; Gurish, Michael ...; visa färre...

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