Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
PLoS One. 2011;6(12):e29537. doi: 10.1371/journal.pone.0029537. Epub 2011 Dec 27.
A well-known role of human peritoneal mesothelial cells (HPMCs), the resident cells of the peritoneal cavity, is the generation of an immune response during peritonitis by activation of T-cells via antigen presentation. Recent findings have shown that intercellular nanotubes (NTs) mediate functional connectivity between various cell types including immune cells - such as T-cells, natural killer (NK) cells or macrophages - by facilitating a spectrum of long range cell-cell interactions. Although of medical interest, the relevance of NT-related findings for human medical conditions and treatment, e.g. in relation to inflammatory processes, remains elusive, particularly due to a lack of appropriate in vivo data. Here, we show for the first time that primary cultures of patient derived HPMCs are functionally connected via membranous nanotubes. NT formation appears to be actin cytoskeleton dependent, mediated by the action of filopodia. Importantly, significant variances in NT numbers between different donors as a consequence of pathophysiological alterations were observable. Furthermore, we show that TNF-α induces nanotube formation and demonstrate a strong correlation of NT connectivity in accordance with the cellular cholesterol level and distribution, pointing to a complex involvement of NTs in inflammatory processes with potential impact for clinical treatment.
人腹膜间皮细胞（HPMCs）是腹腔的固有细胞，其一个众所周知的作用是在腹膜炎期间通过抗原呈递激活 T 细胞来产生免疫反应。最近的研究结果表明，细胞间纳米管（NTs）通过促进一系列长程细胞间相互作用，介导包括免疫细胞（如 T 细胞、自然杀伤（NK）细胞或巨噬细胞）在内的各种细胞类型之间的功能连接。尽管与医学有关，但 NT 相关发现与人类疾病和治疗的相关性，例如与炎症过程的相关性，仍然难以捉摸，特别是由于缺乏适当的体内数据。在这里，我们首次表明，源自患者的原代 HPMCs 可通过膜纳米管实现功能连接。NT 的形成似乎依赖于肌动蛋白细胞骨架，由丝状伪足介导。重要的是，由于病理生理改变，不同供体之间的 NT 数量存在显著差异。此外，我们还表明 TNF-α 诱导纳米管形成，并证明 NT 连接性与细胞胆固醇水平和分布呈强相关性，表明 NT 与炎症过程的复杂关系及其对临床治疗的潜在影响。
