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.

Comparing the Biological Impact of Glatiramer Acetate with the Biological Impact of a Generic

“…This is consistent with literature reports showing that Copaxone positively impacts CD16 + monocytes, [42] and is particularly concerning from a safety perspective because the CD16 dim monocytes favored by generic are known to play a different biological role.…”

Strategies to increase the activity of microglia as efficient protectors of the brain against infections

“…Only monocytes co-expressing CD16 were observed to phagocytose, and addition of IL-10 did not decrease phagocytosis (Pul et al, 2012). Moreover, in primary rat microglia glatiramer acetate promoted the phagocytosis of fluorescent latex beads and increased IL-10 secretion, whereas it decreased the release of TNFα and did not affect NO release (Pul et al, 2011).…”

Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie

“…Beschrieben sind eine Verschiebung von proinflammatorischen Th1-Antworten hin zu eher protektiven Th2-Antworten, eine Modulation antigenpräsentierender Zellen sowie eine gesteigerte Produktion von BDNF mit möglicherweise neuroprotektiven Effekten [24,25,27,34]. Weitere Arbeiten beschreiben auch einen modulierenden Effekt auf Monozyten [52,68]. An immunologisch relevanten Nebenwirkungen sind vereinzelt Lymphknotenschwellungen beschrieben worden.…”