Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2

J. Pablo Abonia, K. Frank Austen, Barrett J. Rollins, Sunil Joshi, Richard A. Flavell, William A. Kuziel, Pandelakis A. Koni, Michael F. Gurish

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Homing of mast cell progenitors (MCps) to the mouse small intestine involves the interaction of α4β7 integrin with mucosal addressin cellular adhesion molecule-1 (MAdCAM-1), We now demonstrate the dependence of this process on CXC chemokine receptor 2 (CXCR2) and vascular cell adhesion molecule-1 (VCAM-1) using null strains and mice sublethally irradiated and bone marrow (BM) reconstituted (SIBR) with wild-type or null BM or with wild-type BM followed by administration of blocking antibody. The intestinal MCp concentration in CXCR2-/- mice was reduced by 67%, but was unaltered in CC chemokine receptor 2-/- (CCR2-/-), CCR3 -/-, or CCR5-/- mice. SIBR mice given CXCR2-/- BM had an intestinal MCp concentration that was 76% less than that in BALB/c BM reconstituted mice. Antibody blockade of VCAM-1 or of CXCR2 in SIBR mice reduced intestinal MCp reconstitution, and mice lacking endothelial VCAM-1 also had a marked reduction relative to wild-type mice. Finally, the half-life of intestinal MCps in wildtype mice was less than one week on the basis of a more than 50% reduction by administration of anti-α4β7 integrin or anti-CXCR2. Thus, the establishment and maintenance of MCps in the small intestine is a dynamic process that requires expression of the α4β7 integrin and the α-chemokine receptor CXCR2.

Original languageEnglish (US)
Pages (from-to)4308-4313
Number of pages6
JournalBlood
Volume105
Issue number11
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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Interleukin-8B Receptors
Chemokine Receptors
Mast Cells
Intestines
Bone
Vascular Cell Adhesion Molecule-1
Integrins
Bone Marrow
CCR2 Receptors
Blocking Antibodies
Small Intestine
Adhesion
Molecules
Antibodies
Half-Life

ASJC Scopus subject areas

  • Hematology

Cite this

Abonia, J. P., Austen, K. F., Rollins, B. J., Joshi, S., Flavell, R. A., Kuziel, W. A., ... Gurish, M. F. (2005). Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2. Blood, 105(11), 4308-4313. https://doi.org/10.1182/blood-2004-09-3578

Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2. / Abonia, J. Pablo; Austen, K. Frank; Rollins, Barrett J.; Joshi, Sunil; Flavell, Richard A.; Kuziel, William A.; Koni, Pandelakis A.; Gurish, Michael F.

In: Blood, Vol. 105, No. 11, 01.06.2005, p. 4308-4313.

Research output: Contribution to journalArticle

Abonia, JP, Austen, KF, Rollins, BJ, Joshi, S, Flavell, RA, Kuziel, WA, Koni, PA & Gurish, MF 2005, 'Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2', Blood, vol. 105, no. 11, pp. 4308-4313. https://doi.org/10.1182/blood-2004-09-3578
Abonia, J. Pablo ; Austen, K. Frank ; Rollins, Barrett J. ; Joshi, Sunil ; Flavell, Richard A. ; Kuziel, William A. ; Koni, Pandelakis A. ; Gurish, Michael F. / Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2. In: Blood. 2005 ; Vol. 105, No. 11. pp. 4308-4313.
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abstract = "Homing of mast cell progenitors (MCps) to the mouse small intestine involves the interaction of α4β7 integrin with mucosal addressin cellular adhesion molecule-1 (MAdCAM-1), We now demonstrate the dependence of this process on CXC chemokine receptor 2 (CXCR2) and vascular cell adhesion molecule-1 (VCAM-1) using null strains and mice sublethally irradiated and bone marrow (BM) reconstituted (SIBR) with wild-type or null BM or with wild-type BM followed by administration of blocking antibody. The intestinal MCp concentration in CXCR2-/- mice was reduced by 67{\%}, but was unaltered in CC chemokine receptor 2-/- (CCR2-/-), CCR3 -/-, or CCR5-/- mice. SIBR mice given CXCR2-/- BM had an intestinal MCp concentration that was 76{\%} less than that in BALB/c BM reconstituted mice. Antibody blockade of VCAM-1 or of CXCR2 in SIBR mice reduced intestinal MCp reconstitution, and mice lacking endothelial VCAM-1 also had a marked reduction relative to wild-type mice. Finally, the half-life of intestinal MCps in wildtype mice was less than one week on the basis of a more than 50{\%} reduction by administration of anti-α4β7 integrin or anti-CXCR2. Thus, the establishment and maintenance of MCps in the small intestine is a dynamic process that requires expression of the α4β7 integrin and the α-chemokine receptor CXCR2.",
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AU - Flavell, Richard A.

AU - Kuziel, William A.

AU - Koni, Pandelakis A.

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