PMID- 17977946
OWN - NLM
STAT- MEDLINE
DCOM- 20080417
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 294
IP  - 2
DP  - 2008 Feb
TI  - MCP-1 targeting inhibits muscularis macrophage recruitment and intestinal smooth 
      muscle dysfunction in colonic inflammation.
PG  - C391-401
AB  - Upregulation of muscularis macrophage numbers and activities plays an important 
      role in the intestinal dysmotility associated with intestinal inflammation. The 
      present study aimed to clarify changes in population dynamics of intestinal 
      muscularis macrophages during colonic inflammation and to test possible 
      inhibitory actions of agents targeting monocyte chemoattractant protein-1 (MCP-1) 
      on muscularis macrophage dynamics and motility disorder in the colonic 
      inflammation elicited by 2,4,6-trinitrobenzene sulfonic acid. In the inflamed 
      muscle layer, ED1 antibody-positive monocytes and monocyte-derived macrophages 
      were increased, followed by increasing resident macrophages positively staining 
      for ED2 antibody. Initiation of the ED1-positive macrophage dynamic is associated 
      with MCP-1 mRNA expression. MCP-1 was expressed in both ED1- and ED2-positive 
      macrophages after inflammation. Electromicroscopic analysis revealed that the 
      cell-division phase of muscularis macrophages was seen only in the early stages 
      of inflammation. In addition, ED1 and ED2 double-positive macrophages can be 
      detected during inflammation. Treatment with dominant negative MCP-1 or 
      neutralizing MCP-1 antibodies markedly inhibited numbers of both ED1- and 
      ED2-positive macrophages. Inflammation-mediated dysmotility was partially 
      recovered by treatment with neutralizing MCP-1 antibodies. These results suggest 
      that the inflamed muscle layer is initially infiltrated by monocytes, which then 
      differentiate and develop into muscularis-resident macrophages. These macrophages 
      express MCP-1 for further recruitment of monocytes. MCP-1 may be one potential 
      therapeutic target for inhibiting intestinal motility disorders in gut 
      inflammation.
FAU - Hori, Masatoshi
AU  - Hori M
AD  - Department of Veterinary Pharmacology, Graduate School of Agriculture and Life 
      Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. 
      ahori@mail.ecc.u-tokyo.ac.jp
FAU - Nobe, Hiromi
AU  - Nobe H
FAU - Horiguchi, Kazuhide
AU  - Horiguchi K
FAU - Ozaki, Hiroshi
AU  - Ozaki H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071031
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Antibodies)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Messenger)
RN  - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Cell Differentiation/drug effects/immunology
MH  - Chemokine CCL2/genetics/*immunology/metabolism
MH  - Chemotaxis, Leukocyte/*immunology
MH  - Colitis/chemically induced/*immunology/physiopathology
MH  - Fluorescent Antibody Technique
MH  - Inflammation Mediators/pharmacology
MH  - Macrophages/*immunology
MH  - Male
MH  - Microscopy, Electron, Transmission
MH  - Monocytes/drug effects/immunology
MH  - Muscle, Smooth/*immunology/pathology/physiopathology
MH  - Myenteric Plexus/immunology/pathology/physiopathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Trinitrobenzenesulfonic Acid/pharmacology
EDAT- 2007/11/06 09:00
MHDA- 2008/04/18 09:00
CRDT- 2007/11/06 09:00
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2008/04/18 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
AID - 00056.2007 [pii]
AID - 10.1152/ajpcell.00056.2007 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2008 Feb;294(2):C391-401. doi: 
      10.1152/ajpcell.00056.2007. Epub 2007 Oct 31.