PMID- 9366570
OWN - NLM
STAT- MEDLINE
DCOM- 19980109
LR  - 20221109
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 100
IP  - 10
DP  - 1997 Nov 15
TI  - Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C 
      chemokine receptor 2 knockout mice.
PG  - 2552-61
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent agonist for mononuclear 
      leukocytes and has been implicated in the pathogenesis of atherosclerosis and 
      granulomatous lung disease. To determine the role of MCP-1 and related family 
      members in vivo, we used homologous recombination in embryonic stem cells to 
      generate mice with a targeted disruption of C-C chemokine receptor 2 (CCR2), the 
      receptor for MCP-1. CCR2-/- mice were born at the expected Mendelian ratios and 
      developed normally. In response to thioglycollate, the recruitment of peritoneal 
      macrophages decreased selectively. In in vitro chemotaxis assays, CCR2-/- 
      leukocytes failed to migrate in response to MCP-1. Granulomatous lung disease was 
      induced in presensitized mice by embolization with beads coupled to purified 
      protein derivative (PPD) of Mycobacterium bovis. As compared with wild-type 
      littermates, CCR2-/- mice had a decrease in granuloma size accompanied by a 
      dramatic decrease in the level of interferon gamma in the draining lymph nodes. 
      Production of interferon gamma was also decreased in PPD-sensitized splenocytes 
      from CCR2-/- mice and in naive splenocytes activated by concanavalin A. We 
      conclude that CCR2-/- mice have significant defects in both delayed-type 
      hypersensitivity responses and production of Th1-type cytokines. These data 
      suggest an important and unexpected role for CCR2 activation in modulating the 
      immune response, as well as in recruiting monocytes/macrophages to sites of 
      inflammation.
FAU - Boring, L
AU  - Boring L
AD  - Gladstone Institute of Cardiovascular Disease, University of California, San 
      Francisco 94141-9100, USA.
FAU - Gosling, J
AU  - Gosling J
FAU - Chensue, S W
AU  - Chensue SW
FAU - Kunkel, S L
AU  - Kunkel SL
FAU - Farese, R V Jr
AU  - Farese RV Jr
FAU - Broxmeyer, H E
AU  - Broxmeyer HE
FAU - Charo, I F
AU  - Charo IF
LA  - eng
GR  - DK-53674/DK/NIDDK NIH HHS/United States
GR  - HL-52773/HL/NHLBI NIH HHS/United States
GR  - HL-56416/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tuberculin)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Chemokine CCL2/pharmacology
MH  - Chemokines/pharmacology
MH  - Chemotaxis, Leukocyte/genetics/*physiology
MH  - Cytokines/*biosynthesis
MH  - Embryo, Mammalian
MH  - Granuloma, Respiratory Tract/immunology/microbiology/physiopathology
MH  - Hematopoietic Stem Cells/cytology/drug effects/physiology
MH  - Humans
MH  - Lung Diseases/immunology/physiopathology
MH  - Lymph Nodes/immunology
MH  - Macrophages, Alveolar/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Monocytes/*physiology
MH  - Mycobacterium bovis
MH  - Receptors, CCR2
MH  - Receptors, CCR5/biosynthesis
MH  - Receptors, Chemokine/biosynthesis/*deficiency/*physiology
MH  - Recombinant Proteins/pharmacology
MH  - Th1 Cells/immunology
MH  - Transcription, Genetic
MH  - Tuberculin
PMC - PMC508456
EDAT- 1997/11/20 07:06
MHDA- 2001/03/28 10:01
PMCR- 1997/11/15
CRDT- 1997/11/20 07:06
PHST- 1997/11/20 07:06 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1997/11/20 07:06 [entrez]
PHST- 1997/11/15 00:00 [pmc-release]
AID - 10.1172/JCI119798 [doi]
PST - ppublish
SO  - J Clin Invest. 1997 Nov 15;100(10):2552-61. doi: 10.1172/JCI119798.