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) ar e potent chemoknes which attract circulating monocytes and neutrophils respectively to inflamed tissues. JE/MCP-1 gene expression has been p reviously studied in rabbit aortae after endothelial denudation and th e rapid appearance of this transcript was thought to precede emigratio n of phagocytes. We now report MCP-1 gene expression following de-endo thelialization of iliac arteries in the pig, a species which can devel op spontaneous atherosclerosis. Using Northern blot analysis, we demon strated 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 l ow 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-r elated gene expressions, urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAl-1). Since smooth muscle cel ls, endothelial cells, and phagocytes are all capable of expressing MC P-1, we examined pig arteries for immunostaining using a monoclonal an tibody to human MCP-1 (5D3-F7). At 8 h after injury, the predominant c ell type staining positive for MCP-1 was the monocyte/macrophage. Stai ning was also observed in occasional scattered neutrophils, but MCP-1 protein could not be detected in smooth muscle cells or on extracellul ar 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 wa ll following injury. The fact that MCP-1 expression accompanied monocy te/macrophage presence in damaged artery, rather than preceding it, is suggestive that continued MCP-1 expression is required for functions other than chemoattraction. (C) 1996 Wiley-Liss, Inc.