Bone Marrow Mesenchymal Stem and Progenitor Cells Induce Monocyte Emigration in Response to Circulating Toll-like Receptor Ligands

被引：401

作者：

Shi, Chao ^{[1
,4
]}

Jia, Ting ^{[1
]}

Mendez-Ferrer, Simon ^{[2
]}

Hohl, Tobias M. ^{[1
]}

Serbina, Natalya V. ^{[1
]}

Lipuma, Lauren ^{[1
]}

Leiner, Ingrid ^{[1
]}

Li, Ming O. ^{[1
]}

Frenette, Paul S. ^{[2
,3
]}

Pamer, Eric G. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Dis Serv, Immunol Program,Sloan Kettering Inst, New York, NY 10065 USA

[2] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA

[3] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA

[4] Weill Cornell Grad Sch Med Sci, Program Immunol & Microbial Pathogenesis, New York, NY 10065 USA

来源：

IMMUNITY | 2011年 / 34卷 / 04期

关键词：

NILE-VIRUS-INFECTION; CHEMOKINE RECEPTOR; INFLAMMATORY MONOCYTES; BACTERIAL-INFECTION; CHEMOATTRACTANT PROTEIN-1; MACROPHAGE RECRUITMENT; IMMUNE-RESPONSE; DENDRITIC CELLS; HOST-DEFENSE; MICE REVEALS;

D O I：

10.1016/j.immuni.2011.02.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：590 / 601

页数：12

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