CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic co-glycolic acid) microparticles and films.
CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic co-glycolic acid) microparticles and films.
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DOI：
10.1039/c6tb02269c
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发表时间：
2017-02-28
期刊：
影响因子：
--
通讯作者：
Liu WF
中科院分区：
文献类型：
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作者：
Chen EY;Chu S;Gov L;Kim YK;Lodoen MB;Tenner AJ;Liu WF
生物相容性是开发用于医疗器械、组织工程和药物递送的生物材料的主要关注点。聚（乳酸-羟基乙酸共聚物）（PLGA）是最广泛使用的可生物降解材料之一，但仍会引发严重的异物反应，影响愈合。包括巨噬细胞在内的免疫细胞对植入的生物材料产生反应，并介导宿主反应，最终可能导致器械失效。以前在我们的实验室中，我们发现CD 200，一种免疫调节蛋白，在体外抑制巨噬细胞炎症激活，并减少生物材料植入物周围的局部免疫细胞浸润。虽然在我们最初的研究中，我们使用聚苯乙烯作为模型材料，但在这里，我们研究了CD 200对PLGA的影响，PLGA是一种具有许多潜在临床应用的常用生物材料。我们制作了不同几何形状的PLGA，用CD 200修饰它们的表面，并检查巨噬细胞细胞因子分泌和吞噬作用。我们发现，CD 200抑制促炎细胞因子TNF-α的分泌，增强抗炎细胞因子IL-10的分泌，表明CD 200在促进伤口愈合和组织重塑中的作用。此外，我们发现，CD 200增加小鼠巨噬细胞和人单核细胞的吞噬作用。总之，这些数据表明，用CD 200修饰导致同时预防炎症和增强吞噬作用的应答。这种免疫调节特征可用作减轻炎症或递送靶向巨噬细胞的药物或抗炎剂的策略。CD 200修饰的PLGA表面抑制炎性细胞因子（TNF-α）分泌，并增强抗炎性细胞因子分泌（IL-10）和巨噬细胞的吞噬作用。
Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant. While in our initial study we used polystyrene as a model material, here we investigate the effect of CD200 on PLGA, a commonly used biomaterial with many potential clinical applications. We fabricated PLGA with varied geometries, modified their surfaces with CD200, and examined macrophage cytokine secretion and phagocytosis. We found that CD200 suppressed secretion of the pro-inflammatory cytokine TNF-α and enhanced secretion of the anti-inflammatory cytokine IL-10, suggesting a role for CD200 in promoting wound healing and tissue remodeling. In addition, we found that CD200 increased phagocytosis in both murine macrophages and human monocytes. Together, these data suggest that modification with CD200 leads to a response that simultaneously prevents inflammation and enhances phagocytosis. This immunomodulatory feature may be used as a strategy to mitigate inflammation or deliver drugs or anti-inflammatory agents targeting macrophages. CD200 modified PLGA surfaces inhibits inflammatory cytokine (TNF-a) secretion, and enhances anti-inflammatory cytokine secretion (IL-10) and phagocytosis by macrophages.