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Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

Connie G. Glasgow, Souheil El-Chemaly, Joel Moss
European Respiratory Review 2012 21: 196-206; DOI: 10.1183/09059180.00009311
Connie G. Glasgow
*Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, #Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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Souheil El-Chemaly
*Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, #Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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Joel Moss
*Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, #Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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  • For correspondence: mossj@nhlbi.nih.gov
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    Figure 1.

    Serum levels of vascular endothelial growth factor (VEGF)-D in lymphangioleiomyomatosis. Serum VEGF-D levels in 111 patients with sporadic lymphangioleiomyomatosis were grouped on the basis of thoracic or abdominal lymphatic involvement (lymphangioleiomyomas and/or adenopathy: presence nequals;77; absence nequals;34) and the presence (nequals;40) or absence (nequals;71) of renal angiomyolipomas (AML). All groups were compared to 40 healthy volunteers. Diamonds: serum measurement of VEGF-D from one patient or healthy volunteer. –––: mean values. #: pequals;0.3; ***: p<0.001. Reproduced from [45] with permission from the publisher.

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    Figure 2.

    Mean annual changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DL,CO) before (white) and after sirolimus (grey) therapy in patients with lymphangioleiomyomatosis. Data show sirolimius therapy resulted in an increase in FVC, FEV1 and DL,CO. Mixed-effect models were used for statistical analysis. #: nequals;18 patients. Reproduced from [76].

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    Figure 3.

    Alveolar lymphangiogenesis is a feature of idiopathic pulmonary fibrosis (IPF). a) Tissue sections reacted with anti-D2-40 (brown) and anti-CD34 (red) antibodies. Lymphatic vessels (D2-40+; black arrows) and blood vessels (CD-34+; red arrows) are visible adjacent to the alveolar spaces (Alv) in early stages of disease. b, c) Presence of hyaluronic acid in IPF lung. Immunofluorescence staining with hyaluronan-binding protein of paraffin-embedded sections of IPF lung tissue shows hyaluronic acid (red) in a representative single confocal microscopy optical section. Fibroblastic areas (*) displaying positive staining for hyaluronic acid are presented as merged images of hyaluronic acid and 4',6-diamidino-2-phenylindole (DAPI; blue) with (b) or without (c) an auto-fluorescence signal (green) and differential influence contrast. Cell nuclei were stained with DAPI. Scale barsequals;50 μm.

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    Figure 4.

    CD11b+ alveolar macrophages in idiopathic pulmonary fibrosis (IPF) develop tube-like structures in vitro. CD11b+ alveolar macrophages were cultured in Matrigel® for up to 31 days and inspected under white light or after fluorescent-labelling of cytoplasm (CellTracker™ Orange CMTMR; Invitrogen, Carlsbad, CA, USA) and nuclei (Hoechst stain; Invitrogen). Large tube-like structures (150 μm in diameter) were observed when cells from subjects with IPF were cultured in Matrigel® (BD Biosciences, San Jose, CA, USA) for 30 days. A series of confocal images were reconstructed in three-dimensional renderings and representative snapshots of tubular structures are presented as overlaid fluorescence a, b) with or c) without differential influence contrast.

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Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis
Connie G. Glasgow, Souheil El-Chemaly, Joel Moss
European Respiratory Review Sep 2012, 21 (125) 196-206; DOI: 10.1183/09059180.00009311

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Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis
Connie G. Glasgow, Souheil El-Chemaly, Joel Moss
European Respiratory Review Sep 2012, 21 (125) 196-206; DOI: 10.1183/09059180.00009311
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    • LYMPHANGIOLEIOMYOMATOSIS
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