Stabilin-1/CLEVER-1, a type 2 macrophage marker, is an adhesion and scavenging molecule on human placental macrophages

Abstract

Stabilin-1/common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) is a multidomain protein present in lymphatic and vascular endothelial cells and type 2 immunosuppressive macrophages. In adults, stabilin-1/CLEVER-1 is a scavenging receptor and an adhesion molecule, but much less is known about its role during development. Here, we studied the expression and functions of macrophage stabilin-1/CLEVER-1 in human placenta and during human ontogeny. Using newly generated mAbs, we found that stabilin-1/CLEVER-1 is expressed on virtually all macrophages in term placenta, both in the decidua and in the placental villi. Placental stabilin-1/CLEVER-1 was involved in the scavenging of Ac-LDL (acetylated low density lipoprotein) and in the uptake of fluorescently labeled model antigen OVA. siRNA-mediated suppression of stabilin-1/CLEVER-1 altered the cytokine profile produced by placental macrophages. Stabilin-1/CLEVER-1 on placental macrophages mediated their adhesion to placental vessels and supported their transmigration through vascular endothelium. Finally, we found that stabilin-1/CLEVER-1 is induced very early in fetal macrophages, high endothelial venules, and lymphatic vessels in multiple lymphatic organs. Together, these data suggest that macrophage stabilin-1/CLEVER-1 can potentially regulate leukocyte migration and scavenging during the development of the placenta and fetus.