title: Glatiramer acetate increases phagocytic activity of human monocytes in vitro and in multiple sclerosis patients.
abstract: Beside its effects on T cells, a direct influence on cells of the myelo-monocytic lineage by GA becomes evident. Recently, we demonstrated that GA drives microglia to adopt properties of type II antigen presenting cells (APC) and increases their phagocytic activity. In the present work, we focused on human blood monocytes in order to examine whether GA may increase phagocytic activity in vivo and to evaluate the molecular mechanisms explaining this new discovered mode of action. Peripheral blood mononuclear cells (PBMC) were obtained using a Biocoll-Isopaque gradient and monocytes were subsequently isolated by using CD14 MicroBeads. Phagocytic activity was determined by flow cytometric measurement of the ingestion of fluorescent beads. Flow cytometry was also used to assess monocytic differentiation and expression of phagocytic receptors. Monocytes of GA treated MS patients exhibited a significantly higher phagocytic activity than those of healthy controls or non-treated MS patients. In vitro, a significant phagocytic response was already detectable after 1 h of GA treatment at the concentrations of 62.5 and 125 µg/ml. A significant increase at all concentrations of GA was observed after 3 h and 24 h, respectively. Only monocytes co-expressing CD16, particularly CD14(++)CD16(+) cells, were observed to phagocytose. Treatment of monocytes with IL-10 and supernatants from GA-treated monocytes did not alter phagocytosis. We observed a decrease in CD11c expression by GA while no changes were found in the expression of CD11b, CD36, CD51/61, CD91, TIM-3, and CD206. In our blocking assays, treatment with anti-CD14, anti-CD16, anti-TIM3, anti-CD210, and particularly anti-CD36 antibodies led to a decrease in phagocytosis. Our results demonstrate a new mechanism of action of GA treatment that augments phagocytic activity of human monocytes in vivo and in vitro. This activity seems to arise from the CD14(++)CD16(+) monocyte subset.
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Refik
authors.initials: R
authors.lastname: Pul
authors.forename: Franco
authors.initials: F
authors.lastname: Morbiducci
authors.forename: Jelena
authors.initials: J
authors.lastname: Škuljec
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.forename: Vikramjeet
authors.initials: V
authors.lastname: Singh
authors.forename: Ute
authors.initials: U
authors.lastname: Diederichs
authors.forename: Niklas
authors.initials: N
authors.lastname: Garde
authors.forename: Elke Verena
authors.initials: EV
authors.lastname: Voss
authors.forename: Corinna
authors.initials: C
authors.lastname: Trebst
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000328:Adult; D017209:Apoptosis; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D000068717:Glatiramer Acetate; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate