Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium.
BACKGROUND
Healing after myocardial infarction is characterized by the presence of macrophages in the infarcted area. Since augmented monocyte influx has been implicated as a potential mechanism for improved healing after reperfusion, we wished to study the induction of monocyte chemoattractant protein-1 (MCP-1) during reperfusion.


RESULTS
The cDNA for MCP-1 was cloned from a canine jugular vein endothelial cell (CJVEC) library and exhibited 78% identity with the deduced amino acid sequence of human MCP-1. Samples of myocardium were taken from control and ischemic segments after 1 hour of ischemia and various times of reperfusion; total RNA was isolated from myocardial samples and probed with a cDNA probe for canine MCP-1. Induction of MCP-1 mRNA occurred only in previously ischemic segments within the first hour of reperfusion, peaked at 3 hours, and persisted throughout the first 2 days of reperfusion. In the absence of reperfusion, no significant MCP-1 induction was seen. Both ischemic (but not preischemic) cardiac lymph and human recombinant TNF-alpha induced MCP-1 in CJVECs. MCP-1 was identified by immunostaining on infiltrating cells and venular (but not arterial) endothelium by 3 hours. In contrast, in situ hybridization showed MCP-1 mRNA to be confined to the endothelium of small veins (venules) 10 to 70 microns in diameter.


CONCLUSIONS
MCP-1 mRNA is induced in the endothelium of a specific class of small veins immediately after reperfusion. MCP-1 induction is confined to the previously ischemic area that has been reperfused. We suggest a significant role for MCP-1 in monocyte trafficking in the reperfused myocardium.
Kumar
A G
AG
Methodist Hospital, DeBakey Heart Center, Department of Medicine, Houston, TX, USA.
Ballantyne
C M
CM
Michael
L H
LH
Kukielka
G L
GL
Youker
K A
KA
Lindsey
M L
ML
Hawkins
H K
HK
Birdsall
H H
HH
MacKay
C R
CR
LaRosa
G J
GJ
Rossen
R D
RD
Smith
C W
CW
Entman
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007601:Jugular Veins / Q000378:metabolism; D008196:Lymph / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D012333:RNA, Messenger / Q000378:metabolism; D014680:Veins
D018932:Chemokine CCL2; D012333:RNA, Messenger