title: 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.
authors.affiliation: MediCity Research Laboratory, Department of Medical Biochemistry and Genetics, University of Turku, and National Institute of Health and Welfare, Turku, Finland.
authors.forename: Senthil
authors.initials: S
authors.lastname: Palani
authors.forename: Mikael
authors.initials: M
authors.lastname: Maksimow
authors.forename: Mari
authors.initials: M
authors.lastname: Miiluniemi
authors.forename: Kaisa
authors.initials: K
authors.lastname: Auvinen
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
mesh_terms: D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D047109:Fetal Development; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D007962:Leukocytes / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply / Q000166:cytology*; D011247:Pregnancy; D034622:RNA Interference; D034741:RNA, Small Interfering; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism*; D057705:Transendothelial and Transepithelial Migration
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D016207:Cytokines; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; D016201:Receptors, Lymphocyte Homing; C449926:STAB1 protein, human; C032629:acetyl-LDL