PURPOSE: To investigate the specific role of very late antigen-1 (VLA-1; also known as integrin α1β1) in corneal inflammatory lymphangiogenesis in vivo and lymphatic endothelial cell functions in vitro. METHODS: A standard suture-induced corneal inflammatory lymphangiogenesis model was used in normal adult BALB/c mice to test the effect of systemic administration of VLA-1-neutralizing antibody on lymphatic formation and macrophage infiltration in vivo. Additionally, a human lymphatic endothelial cell culture system was used to examine the effect of VLA-1 gene depletion on lymphatic endothelial cell functions in vitro using small interfering RNAs. RESULTS: These data demonstrated, for the first time, that VLA-1 blockade significantly suppressed corneal lymphangiogenesis and macrophage infiltration during inflammation. Moreover, VLA-1 gene depletion led to a marked inhibition of lymphatic endothelial cell processes of adhesion, proliferation, and capillary tube formation. CONCLUSIONS: These novel findings together indicate that VLA-1 is critically involved in the processes of lymphangiogenesis. Further investigation on this factor may provide novel therapies for corneal inflammation, transplant rejection, and other lymphatic-related disorders in the body.
PURPOSE: To investigate the specific role of very late antigen-1 (VLA-1; also known as integrin α1β1) in corneal inflammatory lymphangiogenesis in vivo and lymphatic endothelial cell functions in vitro. METHODS: A standard suture-induced corneal inflammatory lymphangiogenesis model was used in normal adult BALB/c mice to test the effect of systemic administration of VLA-1-neutralizing antibody on lymphatic formation and macrophage infiltration in vivo. Additionally, a human lymphatic endothelial cell culture system was used to examine the effect of VLA-1 gene depletion on lymphatic endothelial cell functions in vitro using small interfering RNAs. RESULTS: These data demonstrated, for the first time, that VLA-1 blockade significantly suppressed corneal lymphangiogenesis and macrophage infiltration during inflammation. Moreover, VLA-1 gene depletion led to a marked inhibition of lymphatic endothelial cell processes of adhesion, proliferation, and capillary tube formation. CONCLUSIONS: These novel findings together indicate that VLA-1 is critically involved in the processes of lymphangiogenesis. Further investigation on this factor may provide novel therapies for corneal inflammation, transplant rejection, and other lymphatic-related disorders in the body.
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Authors: Don Yuen; Sammy Grimaldo; Roberto Sessa; Tatiana Ecoiffier; Tan Truong; Eric Huang; Michael Bernas; Sarah Daley; Marlys Witte; Lu Chen Journal: Invest Ophthalmol Vis Sci Date: 2014-04-29 Impact factor: 4.799