title: Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2.
abstract: Homing of mast cell progenitors (MCps) to the mouse small intestine involves the interaction of alpha4beta7 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 wild-type mice was less than one week on the basis of a more than 50% reduction by administration of anti-alpha4beta7 integrin or anti-CXCR2. Thus, the establishment and maintenance of MCps in the small intestine is a dynamic process that requires expression of the alpha4beta7 integrin and the alpha-chemokine receptor CXCR2.
authors.affiliation: Department of Pediatrics, Cincinnati Children's Medical Center, OH, USA.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Abonia
authors.forename: K Frank
authors.initials: KF
authors.lastname: Austen
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: Pandelakis A
authors.initials: PA
authors.lastname: Koni
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gurish
mesh_terms: D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D016023:Integrins / Q000502:physiology; D007422:Intestines / Q000166:cytology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D016023:Integrins; D012333:RNA, Messenger; D023063:Receptors, Interleukin-8B; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7