Transgenic monocyte chemoattractant protein-1 (MCP-1) in pancreatic islets produces monocyte-rich insulitis without diabetes: abrogation by a second transgene expressing systemic MCP-1.
Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attracts monocytes and T lymphocytes in vitro; however, its in vivo functions are poorly understood. To address this question, we constructed transgenic mice expressing MCP-1 controlled by an insulin promoter. These mice developed a chronic insulitic infiltrate composed of F4/80+ monocytes with minor populations of CD4+, CD8+, and B220+ cells. Despite persistent transgene expression, the insulitis never progressed, and blood glucose levels remained normal. Thus, MCP-1 alone is sufficient to elicit a monocytic infiltrate, but not to activate elicited cells. These results differ from those obtained with another transgenic model using the mouse mammary tumor virus long terminal repeat, in which mice expressed substantial MCP-1 in several organs but had no infiltrates. However, mice expressing both transgenes had minimal insulitis, indicating that high systemic levels of MCP-1 prevented monocytes from responding to local MCP-1. Thus, the ability of MCP-1 to elicit monocytic infiltration depends on its being expressed at low levels in an anatomically restricted area.
Grewal
I S
IS
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Rutledge
B J
BJ
Fiorillo
J A
JA
Gu
L
L
Gladue
R P
RP
Flavell
R A
RA
Rollins
B J
BJ
D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D018014:Gene Transfer Techniques; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D010182:Pancreatic Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D018932:Chemokine CCL2