Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Graduate Program in the Biology of Aging, University of Southern California, Los Angeles, CA, USA.
Methods Mol Biol. 2020;2144:161-170. doi: 10.1007/978-1-0716-0592-9_14.
The majority of age-related diseases share common inflammatory mechanisms, a phenomenon which has been described as "inflamm-aging," and genetic variants in immune and inflammatory genes are significantly associated with exceptional human longevity and/or age-related diseases. Consistently, aging is associated with increased macrophage infiltration into tissues. Macrophages are a key component of the innate immune system and the inflammatory response, which accomplish key tasks such as phagocytosis, antigen presentation, and cytokine production. Phagocytosis is the process by which specialized cells that can clear harmful foreign particles, pathogens, and dead or dying cells. Upon phagocytosis, foreign particles are internalized in vesicles, forming phagosomes. Phagosomes go on to fuse with lysosomes, and the ingested particles are neutralized by lysosomal enzymes. Macrophages have two main origins: tissue-resident macrophages differentiate from specific embryonic progenitors, whereas monocyte-derived macrophages differentiate from bone-marrow progenitors. Because of their key role in inflammation and damage repair, macrophages are a key cell type in age-related inflammatory diseases. Here, we describe an efficient method to quantify the phagocytotic ability of two types of primary macrophages in aging mice: bone marrow-derived macrophages (BMDMs) and tissue-resident peritoneal macrophages.
大多数与年龄相关的疾病都有共同的炎症机制，这种现象被描述为“炎症衰老”，免疫和炎症基因中的遗传变异与人类的超长寿命和/或与年龄相关的疾病显著相关。一致地，衰老与巨噬细胞向组织中的浸润增加有关。巨噬细胞是先天免疫系统和炎症反应的关键组成部分，完成吞噬、抗原呈递和细胞因子产生等关键任务。吞噬作用是指能够清除有害的外来颗粒、病原体和死亡或垂死细胞的专门细胞的过程。吞噬作用后，外来颗粒被内吞在小泡中，形成吞噬体。吞噬体继续与溶酶体融合，溶酶体中的酶中和被吞噬的颗粒。巨噬细胞有两个主要来源：组织驻留巨噬细胞从特定的胚胎祖细胞分化而来，而单核细胞衍生的巨噬细胞则从骨髓祖细胞分化而来。由于它们在炎症和损伤修复中的关键作用，巨噬细胞是与年龄相关的炎症性疾病中的关键细胞类型。在这里，我们描述了一种在衰老小鼠中量化两种类型原代巨噬细胞吞噬能力的有效方法：骨髓来源的巨噬细胞（BMDMs）和组织驻留的腹腔巨噬细胞。
