Lymphangiogenesis as a Prerequisite in the Pathogenesis of Lung Fibrosis

Despite increasing knowledge on the cellular and molecular mechanisms involved in pulmonary fibrosis, its therapeutic options are still limited. The study of lymphangiogenesis has contributed to a better understanding of tumor growth and metastasis, with a major impact upon changes in therapeutic strategies and this was followed by the research of lymphatic vessels in other pathological conditions. Some data support the possible role of lymphangiogenesis in the pathogenesis of lung fibrosis. However, at the time of diagnosis for each patient with a fibrotic interstitial lung disease, it is necessary to predict the prognosis and to choose for individual targeted-therapy. Our aim was the characterization of lymphangiogenesis as a useful tool to stratify patients with lung fibrosis. We evaluated the presence, morphology and density of D2-40-positive lymphatic vessels and co-localization of D2-40/Ki67 in pulmonary fibrosis with different degrees of severity and without a specific etiology. Lymphatic vessel density did not correlate with severity grade and ranged between 4.66 to 38.33 vessels/x40 field, with the highest value in degree III of fibrosis. An intense proliferative activity of lymphatic endothelial cells was found in 24% (6 out of 25) of cases. The morphology of lymphatics and the presence of splitting combined with the proliferative activity of endothelial cell pillars suggested two different mechanisms in the formation new lymphatic vessels. Our results support the hypothesis that the activity and ongoing evolution of fibrosis can be predicted through the characterization of lymphangiogenesis but its presence or absence cannot predict the severity of fibrosis.