Interaction between intravenous immunoglobulin (IVIg) and the low-density lipoprotein receptor-related protein 1: a role for transcytosis across the blood brain barrier?
Intravenous immunoglobulin (IVIg) is a therapeutic preparation of plasma-derived human IgG and is increasingly used for the treatment of several neurological inflammatory disorders. However, it is not clear whether the IgG molecules contained in IVIg can actually cross the BBB in treated patients. We recently showed that LRP1, an endocytic receptor involved in transcytosis of several proteins across the BBB was able to interact with IVIg. In the present study, we show that LRP1 is involved in IVIg internalization inside living cells. Our data also suggest that following internalization, IVIg is recycled to the cell surface, raising the possibility that LRP1 can mediate IVIg transcytosis across the BBB. Finally, we show that IVIg-LRP1 interaction leads to LRP1 tyrosine phosphorylation.
Department of Research and Development, Héma-Québec, Québec, Canada.
Dominic Paquin
DP
Proulx
Pascal
P
Rouleau
Isabelle
I
Paré
Marie-Michelle
MM
Vallières-Noël
Renée
R
Bazin
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D016756:Immunoglobulins, Intravenous / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D010766:Phosphorylation / Q000502:physiology; D011973:Receptors, LDL / Q000378:metabolism*; D057900:Transcytosis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D016756:Immunoglobulins, Intravenous; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D014443:Tyrosine