JE Gene Expression in an Animal Model of Acute Arterial Graft Rejection

Abstract

Transplant arteriosclerosis (TA) is an immune mediated vascular injury that results in rapid intimal thickening and parenchymal ischemia. The monocytes that infiltrate the transplanted organ's vessels may mediate this effect. One of the cell signals that may initiate monocyte infiltration in rat models of acute and chronic vessel wall rejection is the product of the JE gene, a potent and selective chemoattractant for monocytes. We used combinedin situhybridization and immunocytochemistry to localize JE gene expression in specific cell types using a rat aortic transplant model of acute arterial graft rejection. Within 3 days of transplantation, there was JE mRNA expression in adventitial mesenchymal cells, probably fibroblasts, and this signal increased until 10 days post-transplantation. During this period, the number of adventitial monocytes, identified by immunocytochemistry, increased around the mesenchymal cells expressing JE. Intimal JE mRNA expression between 7 and 20 days localized to undefined mesenchymal intimal cells and occasionally blood-borne monocytes. There was no JE gene expression detected in the intima after 20 days. JE mRNA expression at 20 days was limited to α-actin-positive vascular smooth muscle cells in the outer aspect of the media. At 40 and 60 days, there was no JE hybridization signal in the media or adventitia despite increasing medial monocyte infiltration. The temporal sequence of JE mRNA expression, starting in the adventitia, intima, and finally the media, preceded or coincided with monocyte/macrophage infiltration. These results support our hypothesis that early JE gene expression may lead to the initial monocyte recruitment in acute vessel wall rejection. Because JE gene expression is downregulated by glucocorticoids, their immunosuppressive effect may be partly due to decreased JE gene expression by transplanted vessels.