title: Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization.
abstract: Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMPs treatment in vitro and in vivo models. LMPs regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic effects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic effect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMPs to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efficiently interfering with both vascular and extravascular components of CNV.
authors.affiliation: Department of Pharmacology, Université de Montréal, Montréal, QC, Canada.|Research Center CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Houda
authors.initials: H
authors.lastname: Tahiri
authors.affiliation: Research Center Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada.
authors.forename: Samy
authors.initials: S
authors.lastname: Omri
authors.affiliation: Research Center CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Université de Montréal, Montréal, QC, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Duhamel
authors.affiliation: Departments of Microbiology and Immunology, Université de Montréal, Montréal, QC, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
authors.affiliation: Departments of Microbiology and Immunology, Université de Montréal, Montréal, QC, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Charles River Laboratories, Senneville, Montreal, QC, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Vezina
authors.affiliation: V&O Services, Saint-Lazare, QC, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Bussières
authors.affiliation: School of Optometry, Université de Montréal, Montréal, QC, Canada.
authors.forename: Elvire
authors.initials: E
authors.lastname: Vaucher
authors.affiliation: Research Center Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada.|Department of Ophthalmology, Université de Montréal, Montréal, QC, Canada.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
authors.affiliation: Department of Pathology and Cell Biology, Université de Montréal, Montréal, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hickson
authors.affiliation: Department of Ophthalmology, Université de Montréal, Montréal, QC, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Hammamji
authors.affiliation: Institut du Cancer de Montréal, CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
authors.affiliation: Institut du Cancer de Montréal, CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Department of Medicine, Université de Montréal, Montréal, QC, Canada.|Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Rodier
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.|Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tremblay
authors.affiliation: Institut du Cancer de Montréal, CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Royal
authors.affiliation: Institut du Cancer de Montréal, CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cailhier
authors.affiliation: Department of Pharmacology, Université de Montréal, Montréal, QC, Canada.|Research Center CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.|Research Center Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada.|Department of Ophthalmology, Université de Montréal, Montréal, QC, Canada.|Department of Pediatrics, Université de Montréal, Montréal, QC, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.affiliation: Department of Pharmacology, Université de Montréal, Montréal, QC, Canada.|Research Center CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.|Department of Pediatrics, Université de Montréal, Montréal, QC, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hardy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D016764:Cell Polarity; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D007834:Lasers; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D000067996:RAW 264.7 Cells
chemical_list: D015415:Biomarkers; D018955:CD36 Antigens