PMID- 18048593
OWN - NLM
STAT- MEDLINE
DCOM- 20080523
LR  - 20131121
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 104
IP  - 3
DP  - 2008 Mar
TI  - Apoptotic myocytes generate monocyte chemoattractant protein-1 and mediate 
      macrophage recruitment.
PG  - 601-9
AB  - The mechanisms by which apoptotic myocytes are removed by macrophages have not 
      been fully elucidated. This study examined whether apoptotic myocytes actively 
      recruit macrophages by generating monocyte chemoattractant protein-1 (MCP-1) in 
      experiments in vitro and in vivo. Neonatal rat cardiac myocytes were incubated 
      for 4 h in the presence or absence of staurosporine (STS, 0.2-1 mumol/l), an 
      apoptosis inducer. Nuclear staining with DAPI showed that STS induced apoptosis 
      in a dose-dependent fashion. STS (1 mumol/l) caused extensive DNA fragmentation 
      and increased caspase-3 activity compared with a serum-deprived control. MCP-1 
      mRNA and protein levels in myocytes increased twofold and fourfold, respectively, 
      on STS treatment, and immunochemical staining revealed that apoptotic myocytes 
      expressed MCP-1. To elucidate the role of MCP-1 expressed in apoptotic myocytes 
      to recruit macrophages/monocytes, rat monocytes were incubated in the supernatant 
      of STS-treated myocytes using a trans-well system. The culture medium of 
      STS-treated myocytes recruited monocytes in a MCP-1-dependent fashion. In 
      addition, experiments were performed in vivo using ischemia-reperfused rat 
      hearts. Rats were subjected to 30 min of ligation of the left coronary artery 
      followed by 24 h of reperfusion. After the reperfusion, in the ischemic border 
      myocardium, 17.1 +/- 1.1% of myocytes were terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end-labeling (TUNEL) positive. Moreover, double 
      staining using the TUNEL technique and immunohistochemistry with MCP-1 antibody 
      showed that 69.8 +/- 3.9% of TUNEL-positive myocytes expressed MCP-1 protein. 
      Concomitantly, activated macrophages infiltrated the areas of apoptosis 
      remarkably. These results suggest that apoptotic myocytes produce MCP-1, which 
      have a critical role in the active recruitment of macrophages.
FAU - Kobara, Miyuki
AU  - Kobara M
AD  - Dept. of Clinical Pharmacology, Kyoto Pharmaceutical University, 5 Misasagi 
      Nakauchi-cho, Yamashina-ku, Kyoto, Japan. kobara@mb.kyoto-phu.ac.jp
FAU - Sunagawa, Nahoko
AU  - Sunagawa N
FAU - Abe, Masaki
AU  - Abe M
FAU - Tanaka, Nana
AU  - Tanaka N
FAU - Toba, Hiroe
AU  - Toba H
FAU - Hayashi, Hironori
AU  - Hayashi H
FAU - Keira, Natsuya
AU  - Keira N
FAU - Tatsumi, Tetsuya
AU  - Tatsumi T
FAU - Matsubara, Hiroaki
AU  - Matsubara H
FAU - Nakata, Tetsuo
AU  - Nakata T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071129
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - H88EPA0A3N (Staurosporine)
SB  - IM
CIN - J Appl Physiol (1985). 2008 Mar;104(3):573-4. PMID: 18174386
MH  - Animals
MH  - Animals, Newborn
MH  - *Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - *Cell Movement
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Culture Media, Conditioned/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Macrophages/*metabolism
MH  - Male
MH  - Monocytes/metabolism
MH  - Myocardial Reperfusion Injury/metabolism/pathology
MH  - Myocytes, Cardiac/drug effects/*metabolism/pathology
MH  - *Paracrine Communication
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Staurosporine/pharmacology
MH  - Up-Regulation
EDAT- 2007/12/01 09:00
MHDA- 2008/05/24 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/05/24 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - 00254.2007 [pii]
AID - 10.1152/japplphysiol.00254.2007 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2008 Mar;104(3):601-9. doi: 
      10.1152/japplphysiol.00254.2007. Epub 2007 Nov 29.