Morelli L, Giambartolomei G H, Prat M I, Castaño E M
Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) and Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Neurosci Lett. 1999 Feb 26;262(1):5-8. doi: 10.1016/s0304-3940(99)00023-3.
Microglial cell involvement in Alzheimer's disease has been related to amyloid beta (A beta) internalization, the release of inflammatory cytokines and the development of neuritic plaques. The human monocyte/macrophage THP-1 cell line has been widely used as a model of human microglial cells. We used THP-1 cells to study the adsorption, internalization and resistance to degradation of A beta1-40 and A beta1-42 isoforms offered at nanomolar concentrations and free of large aggregates, conditions that may mimic a pre-fibrillar stage of A beta in the brain. Under these conditions, A betas did not induce THP-1 activation, as assessed by interleukin-1beta expression. A beta1-42 showed a preferential adsorption and intracellular accumulation as compared to A beta1-40, supporting that competent nuclei for A beta1-42 ordered aggregation may be formed inside microglial cells. In light of the possible neurotoxicity of soluble A beta1-42, we propose that amyloid formation within brain phagocytic cells may be a protective mechanism in early stages of the disease.
小胶质细胞参与阿尔茨海默病与β淀粉样蛋白（Aβ）内化、炎性细胞因子释放以及神经炎性斑块的形成有关。人单核细胞/巨噬细胞THP-1细胞系已被广泛用作人小胶质细胞模型。我们使用THP-1细胞研究了纳摩尔浓度且无大聚集体的Aβ1-40和Aβ1-42异构体的吸附、内化及抗降解能力，这些条件可能模拟了大脑中Aβ的纤维前阶段。在这些条件下，通过白细胞介素-1β表达评估，Aβ并未诱导THP-1激活。与Aβ1-40相比，Aβ1-42表现出优先吸附和细胞内积累，这支持了在小胶质细胞内可能形成Aβ1-42有序聚集的活性核心。鉴于可溶性Aβ1-42可能具有神经毒性，我们提出脑吞噬细胞内的淀粉样蛋白形成可能是该疾病早期阶段的一种保护机制。
