Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation

Peter Baluk, Tuomas Tammela, Erin Ator, Natalya Lyubynska, Marc G Achen, Daniel J Hicklin, Michael Jeltsch, Tatiana Petrova, Bronislaw Pytowski, Steven A Stacker, Seppo Ylä-Herttuala, David G Jackson, Kari Alitalo, Donald M McDonald

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Edema 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.
    Alkuperäiskielienglanti
    LehtiJournal of Clinical Investigation
    Vuosikerta115
    Numero2
    Sivut247-257
    Sivumäärä11
    ISSN0021-9738
    DOI - pysyväislinkit
    TilaJulkaistu - 2005
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Lainaa tätä

    Baluk, P., Tammela, T., Ator, E., Lyubynska, N., Achen, M. G., Hicklin, D. J., ... McDonald, D. M. (2005). Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. Journal of Clinical Investigation, 115(2), 247-257. https://doi.org/10.1172/JCI200522037
    Baluk, Peter ; Tammela, Tuomas ; Ator, Erin ; Lyubynska, Natalya ; Achen, Marc G ; Hicklin, Daniel J ; Jeltsch, Michael ; Petrova, Tatiana ; Pytowski, Bronislaw ; Stacker, Steven A ; Ylä-Herttuala, Seppo ; Jackson, David G ; Alitalo, Kari ; McDonald, Donald M. / Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. Julkaisussa: Journal of Clinical Investigation. 2005 ; Vuosikerta 115, Nro 2. Sivut 247-257.
    @article{c9c39e89a38c4ab8bb2cec3fa7e4fc12,
    title = "Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation",
    abstract = "Edema 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.",
    author = "Peter Baluk and Tuomas Tammela and Erin Ator and Natalya Lyubynska and Achen, {Marc G} and Hicklin, {Daniel J} and Michael Jeltsch and Tatiana Petrova and Bronislaw Pytowski and Stacker, {Steven A} and Seppo Yl{\"a}-Herttuala and Jackson, {David G} and Kari Alitalo and McDonald, {Donald M}",
    year = "2005",
    doi = "10.1172/JCI200522037",
    language = "English",
    volume = "115",
    pages = "247--257",
    journal = "Journal of Clinical Investigation",
    issn = "0021-9738",
    publisher = "AMERICAN SOCIETY FOR CLINICAL INVESTIGATION",
    number = "2",

    }

    Baluk, P, Tammela, T, Ator, E, Lyubynska, N, Achen, MG, Hicklin, DJ, Jeltsch, M, Petrova, T, Pytowski, B, Stacker, SA, Ylä-Herttuala, S, Jackson, DG, Alitalo, K & McDonald, DM 2005, 'Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation', Journal of Clinical Investigation, Vuosikerta 115, Nro 2, Sivut 247-257. https://doi.org/10.1172/JCI200522037

    Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. / Baluk, Peter; Tammela, Tuomas; Ator, Erin; Lyubynska, Natalya; Achen, Marc G; Hicklin, Daniel J; Jeltsch, Michael; Petrova, Tatiana; Pytowski, Bronislaw; Stacker, Steven A; Ylä-Herttuala, Seppo; Jackson, David G; Alitalo, Kari; McDonald, Donald M.

    julkaisussa: Journal of Clinical Investigation, Vuosikerta 115, Nro 2, 2005, s. 247-257.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation

    AU - Baluk, Peter

    AU - Tammela, Tuomas

    AU - Ator, Erin

    AU - Lyubynska, Natalya

    AU - Achen, Marc G

    AU - Hicklin, Daniel J

    AU - Jeltsch, Michael

    AU - Petrova, Tatiana

    AU - Pytowski, Bronislaw

    AU - Stacker, Steven A

    AU - Ylä-Herttuala, Seppo

    AU - Jackson, David G

    AU - Alitalo, Kari

    AU - McDonald, Donald M

    PY - 2005

    Y1 - 2005

    N2 - Edema 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.

    AB - Edema 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.

    U2 - 10.1172/JCI200522037

    DO - 10.1172/JCI200522037

    M3 - Article

    VL - 115

    SP - 247

    EP - 257

    JO - Journal of Clinical Investigation

    JF - Journal of Clinical Investigation

    SN - 0021-9738

    IS - 2

    ER -