Monocyte chemoattractant protein-1 gene expression in injured pig artery coincides with early appearance of infiltrating monocyte/macrophages.
Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are potent chemokines which attract circulating monocytes and neutrophils respectively to inflamed tissues. JE/MCP-1 gene expression has been previously studied in rabbit aortae after endothelial denudation and the rapid appearance of this transcript was thought to precede emigration of phagocytes. We now report MCP-1 gene expression following de-endothelialization of iliac arteries in the pig, a species which can develop spontaneous atherosclerosis. Using Northern blot analysis, we demonstrated that MCP-1 mRNA was rapidly induced in pig arteries at 2 h and continued to increase to reach a maximum at 8 h before returning to low levels at 16-24 h after injury. The increase seen for MCP-1 mRNA at 8 h was also observed for IL-8 mRNA but was not apparent for growth-related gene expressions, urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAI-1). Since smooth muscle cells, endothelial cells, and phagocytes are all capable of expressing MCP-1, we examined pig arteries for immunostaining using a monoclonal antibody to human MCP-1 (5D3-F7). At 8 h after injury, the predominant cell type staining positive for MCP-1 was the monocyte/macrophage. Staining was also observed in occasional scattered neutrophils, but MCP-1 protein could not be detected in smooth muscle cells or on extracellular matrix within the sensitivity constraints posed by our methodology. Our results are consistent with invading monocyte/macrophages having a major input into the production of this chemokine in the arterial wall following injury. The fact that MCP-1 expression accompanied monocyte/macrophage presence in damaged artery, rather than preceding it, is suggestive that continued MCP-1 expression is required for functions other than chemoattraction.
Wysocki
S J
SJ
University of Western Australia, Department of Surgery, Fremantle Hospital, Australia.
Zheng
M H
MH
Smith
A
A
Lamawansa
M D
MD
Iacopetta
B J
BJ
Robertson
T A
TA
Papadimitriou
J M
JM
House
A K
AK
Norman
P E
PE
D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000378:metabolism*; D002404:Catheterization / Q000009:adverse effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D004730:Endothelium, Vascular / Q000293:injuries / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D006965:Hyperplasia; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D016209:Interleukin-8 / Q000235:genetics; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
D018932:Chemokine CCL2; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator