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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.
 Previous Article | Next Article 
Submitted December 9, 2005
Accepted April 19, 2006
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*
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA
Molecular Immunology,Program,Institute of Molecular Medicine and Genetics,Medical College of Georgia
Howard Hughes Medical Institute, Yale University School of Medicine New Haven, CT
* Corresponding author; email: mgurish{at}rics.bwh.harvard.edu.
Normal mouse lung lacks appreciable numbers of mast
cells (MC) or MC progenitors (MCp), yet the appearance
of mature MC in the tracheobronchial epithelial surface
is a characteristic of allergic, T-cell dependent
pulmonary inflammation. We hypothesized that pulmonary
inflammation would recruit MCp to inflamed lung and that
this recruitment would be regulated by distinct adhesion
pathways. Ovalbumin-sensitized and challenged mice had a
>28 fold increase in the number of MCp in the lungs. In
mice lacking endothelial vascular cell adhesion molecule
(VCAM)-1 and in wild type mice administered blocking mAb
to VCAM-1 but not to mucosal addressin (Mad)CAM-1,
recruitment of MCp to the inflamed lung was reduced by
>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 to 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 currently is unique among
inflammatory cells in its partial dependence on
47 integrins for lung recruitment
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