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

AbstractStabilin‐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.