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.

Lymphatic System in Cardiovascular Medicine

“…Blocking VEGFR3 signaling with monoclonal antibodies extended the duration of inflammation, aggravated the inflammation or edema in several experimental models, such as in ultraviolet B irradiation-induced skin inflammation, 155 oxazolone-induced contact hypersensitivity, 156 Mycoplasma pulmonis-induced airway inflammation, 154 chronic inflammatory arthritis 157 and inflammatory bowel disease. 158 Overall, these results indicate that IAL is necessary to mount appropriate inflammatory responses.…”

“…154,160 Unlike blood vessels, the lymphatic vessels do not always completely regress after the removal of an inflammatory stimulus, for instance, in mice after Mycoplasma pulmonis infection, 154 despite administration of steroids. 160 However, in an experimental model of skin inflammation, the formed LN lymphatic vessels almost completely regressed in coordination with changes in LN volume.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…166 Recent results suggest that inflammatory bowel disease models also involve lymphangiogenesis, which can be monitored in the gut wall. …”

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

“…Immune cells have an important role in lymphangiogenesis because inflammatory cells such as monocytes/ macrophage can secret VEGFC and VEGFD, inducing inflammatory lymphangiogenesis (Cursiefen et al 2004, Baluk et al 2005, Iwata et al 2007). We determined the mRNA expression levels of lymphatic-related factors in peripheral blood mononuclear cells (PBMCs), polymorphonuclear neutrophils (PMNs), luteal cells (LCs), LECs, and LyECs ( VEGFC mRNA ( Fig.…”