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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1588-1594.
Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2005-12-012781.
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IMMUNOBIOLOGY
Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung
J. Pablo Abonia,
Jenny Hallgren,
Tatiana Jones,
Tong Shi,
Yuhui Xu,
Pandelakis Koni,
Richard A. Flavell,
Joshua A. Boyce,
K. Frank Austen, and
Michael F. Gurish
From the Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA; Molecular Immunology Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta; and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.
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  7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57BL/6 mice, mAb blocking of  4, 1, or 7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both 41 and 47 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 47 integrins for lung recruitment.
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