TRANSGENIC MONOCYTE-CHEMOATTRACTANT-PROTEIN-1 (MCP-1) IN PANCREATIC-ISLETS PRODUCES MONOCYTE-RICH INSULITIS WITHOUT DIABETES - ABROGATION BY A 2ND TRANSGENE EXPRESSING SYSTEMIC MCP-1

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attr acts monocytes and T lymphocytes in vitro; however, its in vivo functi ons are poorly understood, To address this question, we constructed tr ansgenic mice expressing MCP-1 controlled by an insulin promoter. Thes e mice developed a chronic insulitic infiltrate composed of F4/80(+) m onocytes with minor populations of CD4(+), CD8(+), and B220(+) cells, Despite persistent transgene expression, the insulitis never progresse d, and blood glucose levels remained normal, Thus, MCP-1 alone is suff icient to elicit a monocytic infiltrate, but not to activate elicited cells. These results differ from those obtained with another transgeni c model using the mouse mammary tumor virus long terminal repeat, in w hich mice expressed substantial MCP-1 in several organs but had no inf iltrates, However, mice expressing both transgenes had minimal insulit is, indicating that high systemic levels of MCP-1 prevented monocytes from responding to local MCP-1. Thus, the ability of MCP-1 to elicit m onocytic infiltration depends on its being expressed at low levels in an anatomically restricted area.