Pigment Epithelium-derived Factor (PEDF) Blocks Angiotensin II-induced T Cell Adhesion to Endothelial Cells by Suppressing Intercellular Adhesion Molecule-1

Introduction

Pigment epithelium-derived factor (PEDF) was first isolated from the conditioned media of human retinal pigment epithelial cells with neuronal differentiating activity [1]. Recently, PEDF has been shown to be the most potent inhibitor of angiogenesis in the mammalian eye. PEDF inhibited retinal endothelial cell (EC) growth and migration and suppressed ischemia-induced retinal neovascularization [1], thus suggesting that PEDF could protect against the development and progression of proliferative diabetic retinopathy. However, the protective role for PEDF in early diabetic retinopathy is not fully understood.

Leukocyte adhesion to the capillary endothelium (leukostasis) is a critical event in early diabetic retinopathy, whose process is mainly mediated by intercellular adhesion molecule-1 (ICAM-1) expression [2]. Since the renin-angiotensin system is also postulated to participate in early phase of diabetic retinopathy [3] [4], we investigated whether PEDF could inhibit the angiotensin II (Ang II)-induced ICAM-1 expression in human microvascular ECs in vitro. We also investigated subsequent leukocyte adhesion to human microvascular ECs in vitro.

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