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

Eur J Immunol. 2011 Jul;41(7):2052-63. doi: 10.1002/eji.201041376. Epub 2011 Jun 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Adhesion*
  • Cell Movement
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Endothelial Cells / metabolism
  • Female
  • Fetal Development
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Infant
  • Leukocytes / physiology
  • Lipoproteins, LDL / metabolism
  • Macrophages / cytology*
  • Macrophages / metabolism*
  • Placenta / blood supply
  • Placenta / cytology*
  • Pregnancy
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Lymphocyte Homing / genetics
  • Receptors, Lymphocyte Homing / metabolism*
  • Transendothelial and Transepithelial Migration

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Cytokines
  • Lipoproteins, LDL
  • RNA, Small Interfering
  • Receptors, Lymphocyte Homing
  • STAB1 protein, human
  • acetyl-LDL