Newman Kimberley D, Elamanchili Praveen, Kwon Glen S, Samuel John
3118 Dentistry/Pharmacy Centre, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.
J Biomed Mater Res. 2002 Jun 5;60(3):480-6. doi: 10.1002/jbm.10019.
Dendritic cells are the most potent antigen-presenting cells (APC) and the most effective stimulators of primary T cell responses. Based on the strong influence of the APC on the immune response, we investigated cellular uptake of a biodegradable antigen delivery system, poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, at two sites of injection: intraperitoneal and intradermal. We hypothesized that a fluorescent probe, tetramethylrhodamine labeled dextran, loaded in PLGA microspheres would be taken up by APCs and thereby provide a means for studying cellular uptake of PLGA microspheres in vivo. Phagocytic load and cell phenotype were determined using flow cytometry and confocal laser scanning microscopy. The results revealed cellular uptake of tetramethylrhodamine dextran loaded PLGA microspheres at both injection sites. After intraperitoneal immunization, the predominant cell phagocytosing PLGA microspheres in the peritoneal cavity was the macrophage whereas the intradermal immunization resulted in uptake of PLGA microspheres by dendritic cells. Hence, these results suggest that the profile for cellular uptake varies with the site of injection. More importantly, this study provides direct and conclusive evidence of uptake of PLGA microspheres by the most potent APC, the dendritic cell.
树突状细胞是最强大的抗原呈递细胞（APC），也是原发性T细胞反应最有效的刺激物。基于APC对免疫反应的强大影响，我们研究了一种可生物降解的抗原递送系统——聚（D，L-乳酸-共-乙醇酸）（PLGA）微球在两个注射部位（腹腔内和皮内）的细胞摄取情况。我们假设，负载于PLGA微球中的一种荧光探针——四甲基罗丹明标记的葡聚糖，会被APC摄取，从而为在体内研究PLGA微球的细胞摄取提供一种方法。使用流式细胞术和共聚焦激光扫描显微镜测定吞噬负荷和细胞表型。结果显示，在两个注射部位均有细胞摄取负载四甲基罗丹明葡聚糖的PLGA微球。腹腔内免疫后，腹腔中吞噬PLGA微球的主要细胞是巨噬细胞，而皮内免疫则导致树突状细胞摄取PLGA微球。因此，这些结果表明细胞摄取情况因注射部位而异。更重要的是，本研究提供了最强大的APC即树突状细胞摄取PLGA微球的直接确凿证据。
