Scavenger receptor collectin placenta 1 is a novel receptor involved in the uptake of myelin by phagocytes.
Myelin-containing macrophages and microglia are the most abundant immune cells in active multiple sclerosis (MS) lesions. Our recent transcriptomic analysis demonstrated that collectin placenta 1 (CL-P1) is one of the most potently induced genes in macrophages after uptake of myelin. CL-P1 is a type II transmembrane protein with both a collagen-like and carbohydrate recognition domain, which plays a key role in host defense. In this study we sought to determine the dynamics of CL-P1 expression on myelin-containing phagocytes and define the role that it plays in MS lesion development. We show that myelin uptake increases the cell surface expression of CL-P1 by mouse and human macrophages, but not by primary mouse microglia in vitro. In active demyelinating MS lesions, CL-P1 immunoreactivity was localized to perivascular and parenchymal myelin-laden phagocytes. Finally, we demonstrate that CL-P1 is involved in myelin internalization as knockdown of CL-P1 markedly reduced myelin uptake. Collectively, our data indicate that CL-P1 is a novel receptor involved in myelin uptake by phagocytes and likely plays a role in MS lesion development.
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Jeroen F J
JF
Bogie
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Jo
J
Mailleux
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Elien
E
Wouters
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Winde
W
Jorissen
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Elien
E
Grajchen
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Jasmine
J
Vanmol
Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.|Department of Internal Medicine, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Kristiaan
K
Wouters
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Niels
N
Hellings
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Jack
J
van Horssen
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Tim
T
Vanmierlo
Biomedical Research Institute, Hasselt University/Transnational University Limburg, School of Life Sciences, Diepenbeek, Belgium.
Jerome J A
JJ
Hendriks
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D037222:Collectins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D051116:Receptors, Scavenger / Q000378:metabolism*
C422442:COLEC12 protein, human; C000629107:Colec12 protein, mouse; D037222:Collectins; D051116:Receptors, Scavenger