Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine.
Center for Biological Safety and Research, National Institute of Health Sciences.
Biol Pharm Bull. 2022;45(11):1602-1608. doi: 10.1248/bpb.b22-00108.
Lipopolysaccharide (LPS) treatment induced hemophagocytic lymphohistiocytosis in senescence-accelerated mice (SAMP1/TA-1), but not in senescence-resistant control mice (SAMR1). SAMP1/TA-1 treated with LPS exhibited functional impairment of the hematopoietic microenvironment, which disrupted the dynamics of hematopoiesis. Macrophages are a major component of the bone marrow (BM) hematopoietic microenvironment, which regulates hematopoiesis. Qualitative and quantitative changes in activated macrophages in LPS-treated SAMP1/TA-1 are thought to contribute to the functional deterioration of the hematopoietic microenvironment. Thus, we examined the polarization of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages, and the dynamics of macrophage production in the BM of SAMP1/TA-1 and SAMR1 after LPS treatment. After LPS treatment, the proportions of M1 and M2 macrophages and the numbers of macrophage progenitor (CFU-M) cells increased in both SAMP1/TA-1 and SAMR1. However, compared to the SAMR1, the increase in the M1 macrophage proportion was prolonged, and the increase in the M2 macrophage proportion was delayed. The increase in the number of CFU-M cells was prolonged in SAMP1/TA-1 after LPS treatment. In addition, the levels of transcripts encoding an M1 macrophage-inducing cytokine (interferon-γ) and macrophage colony-stimulating factor were markedly increased, and the increases in the levels of transcripts encoding M2 macrophage-inducing cytokines (interleukin (IL)-4, IL-10, and IL-13) were delayed in SAMP1/TA-1 when compared to SAMR1. Our results suggest that LPS treatment led to the severely imbalanced polarization of activated M1/M2 macrophages accompanied by a prolonged increase in macrophage production in the BM of SAMP1/TA-1, which led to the impairment of the hematopoietic microenvironment, and disrupted the dynamics of hematopoiesis.
脂多糖 (LPS) 处理诱导衰老加速小鼠 (SAMP1/TA-1) 发生噬血细胞性淋巴组织细胞增生症，但不诱导衰老抵抗对照小鼠 (SAMR1)。用 LPS 处理的 SAMP1/TA-1 表现出造血微环境的功能障碍，这破坏了造血动力学。巨噬细胞是骨髓 (BM) 造血微环境的主要组成部分，调节造血。LPS 处理的 SAMP1/TA-1 中激活的巨噬细胞的定性和定量变化被认为有助于造血微环境的功能恶化。因此，我们检查了 LPS 处理的 SAMP1/TA-1 和 SAMR1 中促炎 (M1) 和抗炎 (M2) 巨噬细胞的极化以及 BM 中巨噬细胞生成的动力学。在 LPS 处理后，M1 和 M2 巨噬细胞的比例以及巨噬细胞祖细胞 (CFU-M) 细胞的数量在 SAMP1/TA-1 和 SAMR1 中均增加。然而，与 SAMR1 相比，M1 巨噬细胞比例的增加持续时间延长，M2 巨噬细胞比例的增加延迟。LPS 处理后 SAMP1/TA-1 中 CFU-M 细胞数量的增加持续时间延长。此外，编码 M1 巨噬细胞诱导细胞因子 (干扰素-γ) 和巨噬细胞集落刺激因子的转录本水平明显增加，而编码 M2 巨噬细胞诱导细胞因子 (白细胞介素 (IL)-4、IL-10 和 IL-13) 的转录本水平增加延迟在 SAMP1/TA-1 中与 SAMR1 相比。我们的结果表明，LPS 处理导致 SAMP1/TA-1 的 BM 中激活的 M1/M2 巨噬细胞极化严重失衡，同时巨噬细胞生成持续增加，导致造血微环境受损，破坏了造血动力学。
