title: Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung.
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 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.
authors: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Building, Room 624, 1 Jimmy Fund Way, Boston, MA 02115, USA.
authors: J Pablo
authors: JP
authors: Abonia
authors: Jenny
authors: J
authors: Hallgren
authors: Tatiana
authors: T
authors: Jones
authors: Tong
authors: T
authors: Shi
authors: Yuhui
authors: Y
authors: Xu
authors: Pandelakis
authors: P
authors: Koni
authors: Richard A
authors: RA
authors: Flavell
authors: Joshua A
authors: JA
authors: Boyce
authors: K Frank
authors: KF
authors: Austen
authors: Michael F
authors: MF
authors: Gurish