title: High density lipoprotein stimulated migration of macrophages depends on the scavenger receptor class B, type I, PDZK1 and Akt1 and is blocked by sphingosine 1 phosphate receptor antagonists.
abstract: HDL carries biologically active lipids such as sphingosine-1-phosphate (S1P) and stimulates a variety of cell signaling pathways in diverse cell types, which may contribute to its ability to protect against atherosclerosis. HDL and sphingosine-1-phosphate receptor agonists, FTY720 and SEW2871 triggered macrophage migration. HDL-, but not FTY720-stimulated migration was inhibited by an antibody against the HDL receptor, SR-BI, and an inhibitor of SR-BI mediated lipid transfer. HDL and FTY720-stimulated migration was also inhibited in macrophages lacking either SR-BI or PDZK1, an adaptor protein that binds to SR-BI's C-terminal cytoplasmic tail. Migration in response to HDL and S1P receptor agonists was inhibited by treatment of macrophages with sphingosine-1-phosphate receptor type 1 (S1PR1) antagonists and by pertussis toxin. S1PR1 activates signaling pathways including PI3K-Akt, PKC, p38 MAPK, ERK1/2 and Rho kinases. Using selective inhibitors or macrophages from gene targeted mice, we demonstrated the involvement of each of these pathways in HDL-dependent macrophage migration. These data suggest that HDL stimulates the migration of macrophages in a manner that requires the activities of the HDL receptor SR-BI as well as S1PR1 activity.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Aishah
authors.initials: A
authors.lastname: Al-Jarallah
authors.affiliation: Department of Biochemistry and Biomedical Sciences, and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Biomedical Sciences, and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Leticia
authors.initials: L
authors.lastname: González
authors.affiliation: Department of Biochemistry and Biomedical Sciences, and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Trigatti
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D000068876:Fingolimod Hydrochloride; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010069:Oxadiazoles / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051122:Scavenger Receptors, Class B; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D010069:Oxadiazoles; C514896:PDZK1 protein, mouse; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C503964:SEW2871; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013876:Thiophenes; D037342:Pertussis Toxin; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine