Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan; Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan; Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, 18 Kuriyada Kakemachi, Okazaki, Aichi, 444-0011, Japan.
Lung Cancer. 2018 Nov;125:128-135. doi: 10.1016/j.lungcan.2018.09.011. Epub 2018 Sep 16.
The lung was recently re-discovered as a hematopoietic organ for platelet production in mice. However, evidence for the role of the lung in thrombopoiesis in humans is still limited. In this study, we examined megakaryocytes in the pulmonary and systemic circulation, specifically in pulmonary arterial blood (PAB), venous blood (PVB) and peripheral blood using a newly developed microfluidic platform for rare cell isolation.
We analyzed 23 lung cancer patients who underwent surgery in our institute. PAB and PVB were obtained from the resected lung immediately after surgery. Blood samples were size-selected using a filtration-based microfluidic device and enriched rare cells on glass slide specimens were stained with Papanicolaou (Pap), immunocytochemistry (ICC), and immunofluorescence (IF). Lung tissues were also analyzed by immunohistochemistry.
Pap/ICC/IF showed the presence of abundant CD61+/cytokeratin- giant cells with a megakaryocyte lineage in PAB, but only a few in PVB. These megakaryocytes were found to consist of CD61+/CD41+ immature megakaryocytes and CD61+/CD41- mature megakaryocytes with the potential to produce platelets. These findings were confirmed by the conventional hematological analysis of blood smears stained with Giemsa. In analysis of lung cancer, CD61+ megakaryocytes were observed exclusively in the capillaries of non-cancerous tissue, whereas platelets were selectively observed in the tumor blood vessels of cancerous tissue.
These results indicate that numerous megakaryocytes migrate from systemic bone marrows to accumulate in PAs and arrest of mature megakaryocytes in the capillaries of normal lung, suggesting the possibility that the lung plays a physiological role in the systemic thrombopoiesis in lung cancer patients.
肺部最近被重新发现为小鼠血小板生成的造血器官。然而，关于肺部在人类中的促血小板生成作用的证据仍然有限。在这项研究中，我们使用新开发的微流控平台对稀有细胞进行分离，检查了肺部和全身循环中的巨核细胞，特别是在肺动脉血（PAB）、静脉血（PVB）和外周血中。
我们分析了在我们研究所接受手术的 23 名肺癌患者。手术切除肺部后立即从肺部获得 PAB 和 PVB。使用基于过滤的微流控装置对血液样本进行尺寸选择，并在玻璃载玻片标本上用巴氏染色（Pap）、免疫细胞化学（ICC）和免疫荧光（IF）对稀有细胞进行染色。还对肺组织进行了免疫组织化学分析。
Pap/ICC/IF 显示 PAB 中存在大量 CD61+/细胞角蛋白-的巨核细胞，具有巨核细胞谱系，但 PVB 中只有少数。这些巨核细胞被发现由 CD61+/CD41+未成熟巨核细胞和 CD61+/CD41-成熟巨核细胞组成，具有产生血小板的潜力。这些发现通过用吉姆萨染色的常规血液学分析血涂片得到证实。在肺癌分析中，CD61+巨核细胞仅在非癌组织的毛细血管中观察到，而血小板仅在癌组织的肿瘤血管中选择性观察到。
这些结果表明，大量巨核细胞从全身骨髓迁移到 PAs 中，并在正常肺的毛细血管中成熟巨核细胞停止，这表明肺部在肺癌患者的全身促血小板生成中可能发挥生理作用。
