Intralobular Pulmonary Lymphatic Distribution in Normal Human Lung Using D2-40 Antipodoplanin Immunostaining

Abstract

It has been assumed for a long time that except for limited areas close to respiratory bronchioles or their satellite arteries, there is no evidence of lymphatic vessels deep in the pulmonary lobule. An immunohistochemical study using the D2-40 monoclonal antibody was performed on normal pulmonary samples obtained from surgical specimens, with particular attention to the intralobular distribution of lymphatic vessels. This study demonstrated the presence of lymphatics not only in the connective tissue surrounding the respiratory bronchioles but also associated with intralobular arterioles and/or small veins even less than 50 μm in diameter. A few interlobular lymphatic vessels with a diameter ranging from 10 μm to 20 μm were also observed further away, in interalveolar walls. In conclusion, this study, using the D2-40 monoclonal antibody, demonstrated the presence of small lymphatic channels within the normal human pulmonary lobules, emerging from interalveolar interstitium, and around small blood vessels constituting the paraalveolar lymphatics. This thin intralobular lymphatic network may play a key pathophysiological role in a wide variety of alveolar and interstitial lung diseases and requires further investigation. (J Histochem Cytochem 57:643–648, 2009)

Morphometry Analysis of Lymphatics in Pulmonary Adenocarcinomas With a Lepidic Growth Pattern

“…These findings are in agreement with other observations showing normal lung lymphatic vessels extending into the interalveolar septa (Kambouchner and Bernaudin 2009;Sozio et al 2012). Although Koukourakis et al (2005) did not observe any intratumoral lymphatic network within a series of lung carcinomas with LYVE-1 antibody, we found lymphatic vessel hot spots within the invasive patterns of lung adenocarcinomas.…”

“…In normal lung and the lepidic patterns, the lymphatic vessels were classified according to their location, either in an interlobular septum or interalveolar within the pulmonary lobule. As previously reported for normal lung (Kambouchner and Bernaudin 2009;Sozio et al 2012), these intralobular lymphatic vessels were either associated with interalveolar arterioles or venules, or isolated intralobular septal lymphatic vessels at a distance from interalveolar arterioles or venules.…”

“…Moreover, it must be underscored that the lymphatic network topography in the lepidic growth fraction is comparable to that in the intralobular distribution in normal lung (Kambouchner and Bernaudin 2009;Sozio et al 2012). In contrast, a higher LVD was observed in the invasive fractions of tumors, suggesting that a different network pattern is associated with invasion.…”

Lymphatic and blood microvasculature organisation in pulmonary sarcoid granulomas

“…For immunohistochemistry studies, sections were incubated with mouse monoclonal immunoglobulin (Ig)G antibodies to D2-40, which recognises podoplanin expressed by lymphatic vascular endothelium, anti-CD31, which recognises platelet endothelial cell adhesion molecule-1, and anti-CD34, which recognises a 115-kDa transmembrane glycoprotein [4,5]. The latter two are expressed on blood vascular endothelial cells [5].…”

“…Investigating these close relationships might help improve our understanding the biology of granulomas and also orient therapeutic drug research to achieve better targeted distribution. To address this issue, we systematically analysed the interface between granulomas and the lymphatic network by means of D2-40 immunohistochemical labelling or their blood microvessels with CD34 and CD31 immunolabelling [4,5]. To better discriminate their blood and lymphatic vascular supplies we specifically focused our study on selected isolated granulomas, whose location is predominantly intralobular.…”