The phagocytic ability of macrophages empowers them to enforce innate immunity. RAW264.7, THP-1 and peripheral blood mononuclear cell-derived macrophages display considerable variability with regards to their phagocytic ability. We identify the underlying causes that attenuate the phagocytic abilities of a macrophage. Deformability of the cytoplasm and cortex influences the macrophage's phagocytic ability, and macrophages use the large cell-to-cell variability of their cytoplasmic stiffness to modulate their phagocytic ability. We find that the more-deformable macrophages have a higher phagocytic ability than those that are less deformable. Further, the subcellular spatial variability of cortex stiffness gives rise to more-deformable subdomains on the membrane for pathogen ingestion. We report a previously unknown negative-feedback loop that is triggered by the phagocytic oxidative burst. Macrophages utilize the excess reactive oxygen species to stiffen the cytoplasm, reducing their phagocytic propensity. In organisms, ageing or pathological conditions impair the phagocytic ability of macrophages. Our findings identify the targets that could potentially be utilized for restoring the phagocytic ability of the defunct macrophages.

中文翻译：

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活性氧介导的胞质变硬损害了巨噬细胞的吞噬能力。

巨噬细胞的吞噬能力使它们能够增强先天免疫力。RAW264.7，THP-1和外周血单核细胞衍生的巨噬细胞在吞噬能力方面表现出相当大的可变性。我们确定削弱巨噬细胞吞噬能力的根本原因。细胞质和皮质的可变形性会影响巨噬细胞的吞噬能力，​​而巨噬细胞利用细胞质刚度的较大的细胞间变异性来调节其吞噬能力。我们发现，较不易变形的巨噬细胞而言，更易变形的巨噬细胞具有更高的吞噬能力。此外，皮质刚度的亚细胞空间变异性导致膜上更可变形的亚结构域用于病原体摄入。我们报告了一个以前未知的由吞噬性氧化爆发触发的负反馈回路。巨噬细胞利用过量的活性氧来增强细胞质，从而降低其吞噬倾向。在生物中，衰老或病理状况会损害巨噬细胞的吞噬能力。我们的发现确定了可用于恢复已消失的巨噬细胞吞噬能力的靶标。