title: Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands.
abstract: 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.
authors: Immunology Program, Sloan Kettering Institute, Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Chao
authors: C
authors: Shi
authors: Ting
authors: T
authors: Jia
authors: Simon
authors: S
authors: Mendez-Ferrer
authors: Tobias M
authors: TM
authors: Hohl
authors: Natalya V
authors: NV
authors: Serbina
authors: Lauren
authors: L
authors: Lipuma
authors: Ingrid
authors: I
authors: Leiner
authors: Ming O
authors: MO
authors: Li
authors: Paul S
authors: PS
authors: Frenette
authors: Eric G
authors: EG
authors: Pamer
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002465:Cell Movement; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology* / Q000276:immunology*; D054390:Receptors, CCR2 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: C515335:Ccr2 protein, mouse; D008024:Ligands; D008070:Lipopolysaccharides; D054390:Receptors, CCR2; D051193:Toll-Like Receptors