Caffeic acid inhibits acute hyperhomocysteinemia-induced leukocyte rolling and adhesion in mouse cerebral venules.

ABSTRACT

OBJECTIVE: To investigate the effects and possible mechanisms of CA on acute HHcy-induced leukocyte rolling and adhesion in mouse cerebral venules. METHODS: Male C57 BL/6J mice were injected with DL-Hcy (50 mg/kg) and CA (10 mg/kg). The effect of CA on HHcy-induced leukocyte rolling and adhesion in cerebral vessels was assessed using intravital microscopy. Plasma cytokines and chemokines were evaluated by cytometric bead array. ROS production in HUVECs and adhesion molecule expression on leukocytes were determined by flow cytometry. E-selectin and ICAM-1 expression in cerebrovascular endothelium was detected by immunohistochemistry. CD18 phosphorylation and the Src/PI3K/Akt pathway in leukocytes were determined by confocal microscopy and Western blot. RESULTS: CA inhibited HHcy-elicited leukocyte rolling and adhesion, decreased ROS production in HUVECs, and reduced plasma KC, MIP-2, and MCP-1 levels. CA reduced the E-selectin and ICAM-1 expression on cerebrovascular endothelium and CD11b/CD18 on leukocytes caused by HHcy. Of notice, CA depressed CD18 phosphorylation and the Src/PI3K/Akt pathway in leukocytes. CONCLUSIONS: CA inhibited HHcy-provoked leukocyte rolling and adhesion in cerebral venules, ameliorating adhesion molecule expression and activation, which is related to the suppression of the Src/PI3K/Akt pathway in leukocytes.