The Disappearance of Subpleural and Interlobular Lymphatics in Idiopathic Pulmonary Fibrosis

被引:36
作者
Ebina, Masahito [1 ]
Shibata, Naoko
Ohta, Hiromitsu
Hisata, Shu
Tamada, Tsutomu
Ono, Masao [2 ]
Okaya, Kenta [3 ]
Kondo, Takashi [4 ]
Nukiwa, Toshihiro
机构
[1] Tohoku Univ, Grad Sch Med, Dept Resp Med, Aoba Ku, Sendai, Miyagi 9808574, Japan
[2] Tohoku Univ, Grad Sch Med, Dept Pathol, Sendai, Miyagi 9808574, Japan
[3] Mitani Corp, Visual Syst Div, Tokyo, Japan
[4] Tohoku Univ, Dept Thorac Surg, Inst Dev Aging & Canc, Sendai, Miyagi 9808574, Japan
基金
日本学术振兴会;
关键词
MOLECULAR-MECHANISMS; LYMPHANGIOGENESIS; FLOW; PATHOGENESIS; CLEARANCE; GROWTH; LUNG;
D O I
10.1089/lrb.2010.0008
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: The lymphatics in the interlobular and subpleural parenchyma contribute to alveolar clearance in the lung, but the information on the remodeling of these lymphatics is quite limited in idiopathic pulmonary fibrosis lungs that contain severe fibrosis in these regions. We compared the alteration of these lymphatics and lymphangiogenesis among idiopathic pulmonary fibrosis and nonfibrotic interstitial pneumonias with a better prognosis. Methods and Results: The lung tissue specimens of eighteen patients with idiopathic pulmonary fibrosis (ten surgical biopsies and eight autopsies), six with organizing pneumonia, six with cellular nonspecific interstitial pneumonia, and five normal controls were examined by morphometric analysis of the lymphatics identified by immunohistochemistry. In addition, three-dimensional reconstruction of lymphatics, apoptosis of lymphatic endothelial cells and the cells producing growth factors for lymphangiogenesis were also evaluated. Both the subpleural and the interlobular lymphatics in idiopathic pulmonary fibrosis lungs were significantly decreased in the severe fibroconnective lesions, with rare lymphangiogenesis. The three-dimensional images of the subpleural lymphatics in idiopathic pulmonary fibrosis clearly revealed destruction by fibrosis; apoptosis was observed in these lymphatic endothelial cells. In contrast, organizing pneumonia and cellular nonspecific interstitial pneumonia preserved these lymphatics, and active lymphangiogenesis occurred in the alveolar lesions. Conclusions: These results reveal severe damage of the subpleural and interlobular lymphatics in idiopathic pulmonary fibrosis lungs, and suggest impaired alveolar clearance as another pathogenesis of its refractoriness.
引用
收藏
页码:199 / 207
页数:9
相关论文
共 21 条
  • [1] Molecular regulation of angiogenesis and lymphangiogenesis
    Adams, Ralf H.
    Alitalo, Kari
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (06) : 464 - 478
  • [2] Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth
    Albuquerque, Romulo J. C.
    Hayashi, Takahiko
    Cho, Won Gil
    Kleinman, Mark E.
    Dridi, Sami
    Takeda, Atsunobu
    Baffi, Judit Z.
    Yamada, Kiyoshi
    Kaneko, Hiroki
    Green, Martha G.
    Chappell, Joe
    Wilting, Joerg
    Weich, Herbert A.
    Yamagami, Satoru
    Amano, Shiro
    Mizuki, Nobuhisa
    Alexander, Jonathan S.
    Peterson, Martha L.
    Brekken, Rolf A.
    Hirashima, Masanori
    Capoor, Seema
    Usui, Tomohiko
    Ambati, Balamurali K.
    Ambati, Jayakrishna
    [J]. NATURE MEDICINE, 2009, 15 (09) : 1023 - U74
  • [3] Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation
    Baluk, P
    Tammela, T
    Ator, E
    Lyubynska, N
    Achen, MG
    Hicklin, DJ
    Jeltsch, M
    Petrova, TV
    Pytowski, B
    Stacker, SA
    Ylä-Herttuala, S
    Jackson, DG
    Alitalo, K
    McDonald, DM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) : 247 - 257
  • [4] TGF-β1 is a negative regulator of lymphatic regeneration during wound repair
    Clavin, Nicholas W.
    Avraham, Tomer
    Fernandez, John
    Daluvoy, Sanjay V.
    Soares, Marc A.
    Chaudhry, Arif
    Mehrara, Babak J.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2008, 295 (05): : H2113 - H2127
  • [5] Lymphatic vessel activation in cancer
    Das, Suvendu
    Skobe, Mihaela
    [J]. LYMPHATIC CONTINUUM REVISITED, 2008, 1131 : 235 - 241
  • [6] Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis
    Ebina, M
    Shimizukawa, M
    Shibata, N
    Kimura, Y
    Suzuki, T
    Endo, M
    Sasano, H
    Kondo, T
    Nukiwa, T
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (11) : 1203 - 1208
  • [7] Ebina Masahito, 2008, Allergol Int, V57, P165, DOI 10.2332/allergolint.O-07-497
  • [8] Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms
    El-Chemaly, Souheil
    Malide, Daniela
    Zudaire, Enrique
    Ikeda, Yoshihiko
    Weinberg, Benjamin A.
    Pacheco-Rodriguez, Gustavo
    Rosas, Ivan O.
    Aparicio, Marta
    Ren, Ping
    MacDonald, Sandra D.
    Wu, Hai-Ping
    Nathan, Steven D.
    Cuttitta, Frank
    McCoy, J. Philip
    Gochuico, Bernadette R.
    Moss, Joel
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (10) : 3958 - 3963
  • [9] European Respiratory Society, 2002, Am J Respir Crit Care Med, V165, P277, DOI [10.1164/ajrccm.165.2.ats01, DOI 10.1164/AJRCCM.165.2.ATS01]
  • [10] Lymphatic vessels: Pressure- and flow-dependent regulatory reactions
    Gashev, Anatoliy A.
    [J]. LYMPHATIC CONTINUUM REVISITED, 2008, 1131 : 100 - 109