02389nas a2200289   4500008004100000245009100041210006900132260001400201300001300215490000800228520151500236100001701751700002001768700001501788700002301803700001901826700002301845700002101868700002401889700002401913700002301937700002601960700002201986700001802008700002402026856004902050       2005                        eng d00aPathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation0 aPathogenesis of persistent lymphatic vessel hyperplasia in chron  c2005/Feb/  a247 - 570 v1153 aEdema occurs in asthma and other inflammatory diseases when the rate of plasma leakage from blood vessels exceeds the drainage through lymphatic vessels and other routes. It is unclear to what extent lymphatic vessels grow to compensate for increased leakage during inflammation and what drives the lymphangiogenesis that does occur. We addressed these issues in mouse models of (a) chronic respiratory tract infection with Mycoplasma pulmonis and (b) adenoviral transduction of airway epithelium with VEGF family growth factors. Blood vessel remodeling and lymphangiogenesis were both robust in infected airways. Inhibition of VEGFR-3 signaling completely prevented the growth of lymphatic vessels but not blood vessels. Lack of lymphatic growth exaggerated mucosal edema and reduced the hypertrophy of draining lymph nodes. Airway dendritic cells, macrophages, neutrophils, and epithelial cells expressed the VEGFR-3 ligands VEGF-C or VEGF-D. Adenoviral delivery of either VEGF-C or VEGF-D evoked lymphangiogenesis without angiogenesis, whereas adenoviral VEGF had the opposite effect. After antibiotic treatment of the infection, inflammation and remodeling of blood vessels quickly subsided, but lymphatic vessels persisted. Together, these findings suggest that when lymphangiogenesis is impaired, airway inflammation may lead to bronchial lymphedema and exaggerated airflow obstruction. Correction of defective lymphangiogenesis may benefit the treatment of asthma and other inflammatory airway diseases.1 aBaluk, Peter1 aTammela, Tuomas1 aAtor, Erin1 aLyubynska, Natalya1 aAchen, Marc, G1 aHicklin, Daniel, J1 aJeltsch, Michael1 aPetrova, Tatiana, V1 aPytowski, Bronislaw1 aStacker, Steven, A1 aYlä-Herttuala, Seppo1 aJackson, David, G1 aAlitalo, Kari1 aMcDonald, Donald, M  uhttp://view.ncbi.nlm.nih.gov/pubmed/15668734