Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
Am J Physiol Cell Physiol. 2021 Sep 1;321(3):C607-C614. doi: 10.1152/ajpcell.00222.2021. Epub 2021 Aug 11.
Bovine milk exosomes (BMEs) are being explored in drug delivery despite their rapid elimination by macrophages. We aimed at identifying the BME transporter in murine bone marrow-derived macrophages (BMDMs). Fluorophore-labeled BMEs were used in transport studies in BMDMs from C57BL/6J and class A scavenger receptor type 1/2 (CASR-1/2) knockout mice and tissue accumulation in macrophage-depleted C57BL/6J mice. Parametric and nonparametric statistics tests for pairwise and multiple comparisons were used. Chemical inhibitors of phagocytosis by cytochalasin D led to a 69 ± 18% decrease in BME uptake compared with controls ( < 0.05), whereas inhibitors of endocytic pathways other than phagocytosis had a modest effect on uptake ( > 0.05). Inhibitors of class A scavenger receptors (CASRs) including CASR-1/2 caused a 70% decrease in BME uptake ( < 0.05). The uptake of BMEs by BMDMs from CASR-1/2 knockout mice was smaller by 58 ± 23% compared with wild-type controls ( < 0.05). Macrophage depletion by clodronate caused a more than 44% decrease in BME uptake in the spleen and lungs ( < 0.05), whereas the decrease observed in liver was not statistically significant. In conclusion, CASR-1/2 facilitates the uptake of BMEs in BMDMs and C57BL/6J mice.
牛源外泌体（BMEs）在药物递送中得到了广泛研究，尽管它们会被巨噬细胞迅速清除。我们旨在鉴定鼠源骨髓来源巨噬细胞（BMDMs）中的 BME 转运体。荧光标记的 BME 用于 C57BL/6J 和 A 类清道夫受体 1/2（CASR-1/2）敲除鼠的 BMDM 转运研究，并在巨噬细胞耗竭的 C57BL/6J 小鼠中进行组织累积研究。采用参数和非参数统计检验进行两两和多重比较。细胞松弛素 D 等吞噬作用的化学抑制剂与对照组相比，BME 摄取减少了 69±18%（ < 0.05），而吞噬作用以外的其他内吞途径抑制剂对摄取的影响较小（ > 0.05）。包括 CASR-1/2 在内的 A 类清道夫受体（CASRs）抑制剂使 BME 摄取减少了 70%（ < 0.05）。与野生型对照相比，CASR-1/2 敲除鼠的 BMDM 对 BME 的摄取减少了 58±23%（ < 0.05）。氯膦酸盐引起的巨噬细胞耗竭导致脾脏和肺部的 BME 摄取减少超过 44%（ < 0.05），而肝脏中的减少没有统计学意义。总之，CASR-1/2 促进了 BMDMs 和 C57BL/6J 小鼠对 BME 的摄取。
