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Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands.

Inflammatory (Ly6C(hi) CCR2+) monocytes provide defense against infections but also contribute to autoimmune diseases and atherosclerosis. Monocytes originate from bone marrow and their entry into the bloodstream requires stimulation of CCR2 chemokine receptor by monocyte chemotactic protein-1 (MCP1). How monocyte emigration from bone marrow is triggered by remote infections remains unclear. We demonstrated that low concentrations of Toll-like receptor (TLR) ligands in the bloodstream drive CCR2-dependent emigration of monocytes from bone marrow. Bone marrow mesenchymal stem cells (MSCs) and their progeny, including CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells, rapidly expressed MCP1 in response to circulating TLR ligands or bacterial infection and induced monocyte trafficking into the bloodstream. Targeted deletion of MCP1 from MSCs impaired monocyte emigration from bone marrow. Our findings suggest that bone marrow MSCs and CAR cells respond to circulating microbial molecules and regulate bloodstream monocyte frequencies by secreting MCP1 in proximity to bone marrow vascular sinuses.

Pubmed ID: 21458307

Authors

  • Shi C
  • Jia T
  • Mendez-Ferrer S
  • Hohl TM
  • Serbina NV
  • Lipuma L
  • Leiner I
  • Li MO
  • Frenette PS
  • Pamer EG

Journal

Immunity

Publication Data

April 22, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: 5P01CA023766-31
  • Agency: NIAID NIH HHS, Id: 5R37AI039031
  • Agency: NIAID NIH HHS, Id: K08 AI071998
  • Agency: NIAID NIH HHS, Id: K08 AI071998-02
  • Agency: NIAID NIH HHS, Id: K08 AI071998-03
  • Agency: NIAID NIH HHS, Id: K08AI071998
  • Agency: NCI NIH HHS, Id: P01 CA023766
  • Agency: NCI NIH HHS, Id: P01 CA023766-30
  • Agency: NCI NIH HHS, Id: P01 CA023766-31
  • Agency: NIAID NIH HHS, Id: R01 AI080619
  • Agency: NIDDK NIH HHS, Id: R01 DK056638
  • Agency: NIDDK NIH HHS, Id: R01 DK056638-05
  • Agency: NHLBI NIH HHS, Id: R01 HL069438
  • Agency: NHLBI NIH HHS, Id: R01 HL097819
  • Agency: NHLBI NIH HHS, Id: R01 HL097819-03
  • Agency: NIDDK NIH HHS, Id: R01DK056638
  • Agency: NHLBI NIH HHS, Id: R01HL097819
  • Agency: NIAID NIH HHS, Id: R37 AI039031
  • Agency: NIAID NIH HHS, Id: R37 AI039031-12
  • Agency: NIAID NIH HHS, Id: R37 AI039031-13
  • Agency: NIAID NIH HHS, Id: R37 AI039031-14
  • Agency: NIAID NIH HHS, Id: R37 AI039031-15
  • Agency: NIAID NIH HHS, Id: R37 AI039031-16

Mesh Terms

  • Animals
  • Bone Marrow
  • Cell Movement
  • Ligands
  • Lipopolysaccharides
  • Mesenchymal Stromal Cells
  • Mice
  • Mice, Inbred C57BL
  • Monocytes
  • Receptors, CCR2
  • Toll-Like Receptors