α4β7 integrin is required for the inflammatory recruitment of mast cell progenitors to the lung

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α4β7 Integrin Is Required for the Inflammatory Recruitment of Mast Cell Progenitors to the Lung J. P. Abonia, M. F. Gurish, D. S. Friend, K. F. Austen, J. A. Boyce; Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, MA. RATIONALE: Phenotypically heterogeneous populations of mast cells (MCs) originate from a single bone marrow derived precursor (MCp) that lacks distinctive granules. Although allergic or helminth induced mucosal inflammation involves reactive MC hyperplasia, the responsible mechanisms are incompletely studied. METHODS: Using a limiting dilution and MC colony formation assay, we evaluated changes in MCp number in the lung due to T-helper Class 2 polarized immune responses. As mature MC are increased during inflammation, we wished to test the hypothesis that this increase was due to an influx of MCp. We induced pulmonary inflammation by ip sensitization of mice with ovalbumin in alum, followed by aerosolized ovalbumin challenge. RESULTS: A ~5 fold increase in MCp concentration was detectable in the lung after 3 days of challenge in sensitized BALB/c or C57BL/6 mice. Continued challenge enhanced the MCp yield and resulted in the appearance of mature MC in the lung. Although β7-integrin deficient mice had normal numbers of baseline MCp in their lung, these mice exhibited a 65% reduction in ovalbumin induced pulmonary MCp recruitment which was not apparent in either their +/+ controls or αε-deficient mice. CONCLUSIONS: Taken together, these findings demonstrate distinct integrin requirements for basal and inflammation induced MCp recruitment to the lung, and specifically implicate the α4β7 integrin heterodimer as a requirement for the inflammatory recruitment of MCp to the lung. Funding: National Institutes of Health

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J ALLERGY CLIN IMMUNOL FEBRUARY 2004