Hitoshi Dejima1, Hayao Nakanishi2, Hiroaki Kuroda3, Mayumi Yoshimura4, Noriaki Sakakura5, Nanae Ueda6, Yuko Ohta7, Rie Tanaka8, Sayomi Mori9, Tatsuya Yoshida10, Toyoaki Hida11, Noriyoshi Sawabata12, Yasushi Yatabe13, Yukinori Sakao14. 1. 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. Electronic address: Hdejima@mdanderson.org. 2. 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. Electronic address: hnakanis@aichi-cc.jp. 3. Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: h-kuroda@aichi-cc.jp. 4. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: m_yoshimura@aichi-cc.jp. 5. Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: nsakakura@aichi-cc.jp. 6. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: nueda@aichi-cc.jp. 7. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: hdejima@aichi-cc.jp. 8. Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, 18 Kuriyada Kakemachi, Okazaki, Aichi, 444-0011, Japan. Electronic address: hdejim@aichi-cc.jp. 9. Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, 18 Kuriyada Kakemachi, Okazaki, Aichi, 444-0011, Japan. Electronic address: kentaikensa@acc-aichi.com. 10. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: t.yoshida@aichi-cc.jp. 11. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: 107974@aichi-cc.jp. 12. Department of Thoracic and Cardiovascular Surgery, Nara Medical University School of Medicine, 840, Shijo-cho, Kashihara, Nara, 634-8521, Japan. Electronic address: nsawabata@naramed-u.ac.jp. 13. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: yyatabe@aichi-cc.jp. 14. Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address: ysakao@med.teikyo-u.ac.jp.
Abstract
OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: 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. MATERIALS AND METHODS: We analyzed 23 lung cancerpatients 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. RESULTS: 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. CONCLUSIONS: 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 cancerpatients.
Authors: Paulina Valadez-Cosmes; Kathrin Maitz; Oliver Kindler; Sofia Raftopoulou; Melanie Kienzl; Ana Santiso; Zala Nikita Mihalic; Luka Brcic; Jörg Lindenmann; Melanie Fediuk; Martin Pichler; Rudolf Schicho; A McGarry Houghton; Akos Heinemann; Julia Kargl Journal: Front Immunol Date: 2021-08-13 Impact factor: 7.561