PMID- 18977759
OWN - NLM
STAT- MEDLINE
DCOM- 20090212
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 51
DP  - 2008 Dec 19
TI  - Role of CC chemokine receptor 2 in bone marrow cells in the recruitment of 
      macrophages into obese adipose tissue.
PG  - 35715-23
LID - 10.1074/jbc.M804220200 [doi]
AB  - The MCP-1 (monocyte chemoattractant protein-1)/CCR2 (CC motif chemokine 
      receptor-2) pathway may play a role in macrophage infiltration into obese adipose 
      tissue. Here we investigated the role of CCR2 in the recruitment of bone 
      marrow-derived macrophages into obese adipose tissue in vitro and in vivo. Using 
      the TAXIScan device, which can measure quantitatively the directionality and 
      velocity of cell migration at time lapse intervals in vitro, we demonstrated that 
      bone marrow cells (BMCs) from wild type mice migrate directly toward MCP-1 or 
      culture medium conditioned by adipose tissue explants of genetically obese ob/ob 
      mice, which are efficiently suppressed by pharmacological blockade of CCR2 
      signaling. The number of F4/80-positive macrophages was reduced in the adipose 
      tissue from high fat diet-fed obese KKAy or ob/ob mice treated with a CCR2 
      antagonist propagermanium relative to vehicle-treated groups. We also found that 
      the number of macrophages is reduced in the adipose tissue from ob/ob mice 
      reconstituted with CCR2(-/-) BMCs (ob/ob + CCR2(-/-) BMCs) relative to those with 
      CCR2+/+ BMCs (ob/ob + CCR2+/+ BMCs). Expression of mRNAs for CD11c and TLR4 
      (Toll-like receptor 4) markers of proinflammatory M1 macrophages was also 
      decreased in the adipose tissue from ob/ob + CCR2(-/-) BMCs relative to ob/ob + 
      CCR2+/+ BMCs, whereas mannose receptor and CD163, markers of anti-inflammatory M2 
      macrophages, were unchanged. This study provides in vivo and in vitro evidence 
      that CCR2 in bone marrow cells plays an important role in the recruitment of 
      macrophages into obese adipose tissue.
FAU - Ito, Ayaka
AU  - Ito A
AD  - Department of Molecular Medicine and Metabolism, Medical Research Institute, 
      Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8510, Japan.
FAU - Suganami, Takayoshi
AU  - Suganami T
FAU - Yamauchi, Akira
AU  - Yamauchi A
FAU - Degawa-Yamauchi, Mikako
AU  - Degawa-Yamauchi M
FAU - Tanaka, Miyako
AU  - Tanaka M
FAU - Kouyama, Ryuji
AU  - Kouyama R
FAU - Kobayashi, Yuko
AU  - Kobayashi Y
FAU - Nitta, Nao
AU  - Nitta N
FAU - Yasuda, Kazuki
AU  - Yasuda K
FAU - Hirata, Yukio
AU  - Hirata Y
FAU - Kuziel, William A
AU  - Kuziel WA
FAU - Takeya, Motohiro
AU  - Takeya M
FAU - Kanegasaki, Shiro
AU  - Kanegasaki S
FAU - Kamei, Yasutomi
AU  - Kamei Y
FAU - Ogawa, Yoshihiro
AU  - Ogawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081030
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (CD11c Antigen)
RN  - 0 (CD163 antigen)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adipose Tissue/*metabolism/pathology
MH  - Animals
MH  - Antigens, CD/genetics/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/genetics/metabolism
MH  - Bone Marrow Cells/*metabolism/pathology
MH  - CD11c Antigen/genetics/metabolism
MH  - *Cell Movement
MH  - Chemokine CCL2/genetics/metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lectins, C-Type/genetics/metabolism
MH  - Macrophages/*metabolism/pathology
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - Obesity/genetics/*metabolism/pathology
MH  - Receptors, CCR2/genetics/*metabolism
MH  - Receptors, Cell Surface/genetics/metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
EDAT- 2008/11/04 09:00
MHDA- 2009/02/13 09:00
CRDT- 2008/11/04 09:00
PHST- 2008/11/04 09:00 [entrez]
PHST- 2008/11/04 09:00 [pubmed]
PHST- 2009/02/13 09:00 [medline]
AID - S0021-9258(20)58515-3 [pii]
AID - 10.1074/jbc.M804220200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Dec 19;283(51):35715-23. doi: 10.1074/jbc.M804220200. Epub 2008 
      Oct 30.