In our study, the expressions of the macrophage marker F4/80 and the typical pro-angiogenic factor IL-1β were increased significantly in the corneas of K14-Angptl2 mice compared to the expressions in their background strain (
Fig. 2). It has been reported that the extravasation of monocyte-macrophage lineage cells from limbal vessels to corneal stroma is regulated through integrin α5β1,
27,28 which is a functional receptor of Angptl2.
18 Further, Angptl2 was shown to activate an inflammatory cascade in endothelial cells and promote their migration through integrin α5β1 receptor, thereby inducing the chemotaxis of monocytes and macrophages.
18 Furthermore, integrin α5β1 signaling activated NF-κB cascade and accelerated various inflammatory cytokines, including IL-1β.
29 Taken together, our results highlighted the functional role of Angptl2–integrin α5β1 interaction in corneal inflammation. Corroborating the results of a previous study by Muether et al. who reported that integrin α5β1 is upregulated during corneal angiogenesis, and that its inhibition by antagonist caused prevention and regression of corneal NV,
30 our study demonstrated a significant reduction in the expression of the F4/80 and IL-1β in the corneas of Angptl2
−/− mice compared to their background strains (
Fig. 3). Interestingly, Dietrich et al. reported that corneal lymphatic vessels expressed α5 integrin and corneal lymphangiogenesis also was mediated through α5 integrin.
31,32 Because monocyte-macrophage lineage cells participate in the neovascularization process, fewer F4/80-positive cells in the corneas of Angptl2
−/− mice may, at least in part, explain the promotion mechanisms of inflammatory corneal hemangiogenesis and lymphangiogenesis by Angptl2.