Mast cells (MCs) are centrally important in allergic inflammation of the airways, as well as in the intestinal immune response to helminth infection. A single lineage of bone marrow (BM)-derived progenitors emigrates from the circulation and matures into phenotypically distinct MCs in different tissues. Because the mechanisms of MC progenitor (MCp) homing to peripheral tissues have not been evaluated, we used limiting dilution analysis to measure the concentration of MCp in various tissues of mice deficient for candidate homing molecules. MCp were almost completely absent in the small intestine but were present in the lung, spleen, BM, and large intestine of β7 integrin-deficient mice (on the C57BL/6 background), indicating that a β7 integrin is critical for homing of these cells to the small intestine. MCp concentrations were not altered in the tissues of mice deficient in the αE integrin (CD103), the β2 integrin (CD18), or the recombination activating gene (RAG)-2 gene either alone or in combination with the interleukin (IL)-receptor common γ chain. Therefore, it is the α4β7 integrin and not the αEβ7 integrin that is critical, and lymphocytes and natural killer cells play no role in directing MCp migration under basal conditions. When MCp in BALB/c mice were eliminated with sublethal doses of γ-radiation and then reconstituted with syngeneic BM, the administration of anti-α4β7 integrin, anti-α4 integrin, anti-β7 integrin, or anti–MAdCAM-1 monoclonal antibodies (mAbs) blocked the recovery of MCp in the small intestine. The blocking mAbs could be administered as late as 4 d after BM reconstitution with optimal inhibition, implying that the MCp must arise first in the BM, circulate in the vasculature, and then translocate into the intestine. Inasmuch as MCp are preserved in the lungs of β7 integrin-deficient and anti-α4β7 integrin-treated mice but not in the small intestine, α4β7 integrin is critical for tissue specific extravasation for localization of MCp in the small intestine, but not the lungs.
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5 November 2001
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October 29 2001
Intestinal Mast Cell Progenitors Require CD49dβ7 (α4β7 Integrin) for Tissue-specific Homing
Michael F. Gurish,
Michael F. Gurish
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
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Hong Tao,
Hong Tao
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
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J. Pablo Abonia,
J. Pablo Abonia
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
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Anu Arya,
Anu Arya
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
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Daniel S. Friend,
Daniel S. Friend
2Department of Pathology, Harvard Medical School, Boston, MA 02115
4Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115
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Christina M. Parker,
Christina M. Parker
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
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K. Frank Austen
K. Frank Austen
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
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Michael F. Gurish
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
Hong Tao
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
J. Pablo Abonia
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
Anu Arya
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
Daniel S. Friend
2Department of Pathology, Harvard Medical School, Boston, MA 02115
4Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115
Christina M. Parker
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
K. Frank Austen
1Department of Medicine, Harvard Medical School, Boston, MA 02115
3Division of Rheumatology, Immunology and Allergy
Address correspondence to Dr. M.F. Gurish, Smith Research Building, Room 616, One Jimmy Fund Way, Harvard Medical School, Boston, MA 02115. Phone: 617-525-1235; Fax: 617-525-1310; E-mail: [email protected]
*
Abbreviations used in this paper: BM, bone marrow; BMMC, bone marrow-derived MC; ICAM, intercellular adhesion molecule; MC, mast cell; MCp, MC progenitor; MMC, reactive or mucosal MC; MNC, mononuclear cell; SCF, stem cell factor.
Received:
April 27 2001
Revision Received:
August 16 2001
Accepted:
September 06 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2001
J Exp Med (2001) 194 (9): 1243–1252.
Article history
Received:
April 27 2001
Revision Received:
August 16 2001
Accepted:
September 06 2001
Citation
Michael F. Gurish, Hong Tao, J. Pablo Abonia, Anu Arya, Daniel S. Friend, Christina M. Parker, K. Frank Austen; Intestinal Mast Cell Progenitors Require CD49dβ7 (α4β7 Integrin) for Tissue-specific Homing . J Exp Med 5 November 2001; 194 (9): 1243–1252. doi: https://doi.org/10.1084/jem.194.9.1243
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