Expression and regulation of activated leukocyte cell adhesion molecule in human retinal vascular endothelial cells

Abstract

Activated leukocyte cell adhesion molecule (ALCAM; CD166) is an immunoglobulin superfamily member that has been described in several non-ocular endothelial populations, but not in relation to endothelium within the eye. Studies in extraocular systems have implicated ALCAM in angiogenesis and leukocyte transendothelial migration, which are key processes in retinal vascular diseases. We investigated the expression of ALCAM in human retinal endothelium, and studied the regulation of expression by established angiogenic and inflammatory stimuli. Retinal endothelial expression of ALCAM was detected in primary retinal endothelial cultures isolated from human cadavers by RT-PCR (n = 4 donors) and Western blot (n = 4 donors), and in intact human retina by immunohistochemistry (n = 3 donors). In the 4 donors studied by RT-PCR, transcript encoding the truncated soluble isoform, sALCAM, was also detected. Quantitative real-time RT-PCR demonstrated significant up-regulation of ALCAM and sALCAM in response to stimulation with master cytokine, tumor necrosis factor (TNF)-α. However, general inflammatory stimulus, lipopolysaccharide (LPS), and the prototype Th1, Th2 and Th17 cytokines, interferon (IFN)-γ, interleukin (IL)-4 and IL-17A, respectively, did not impact ALCAM or sALCAM expression. In contrast, expression of ALCAM was significantly up-regulated by vascular endothelial growth factor (VEGF)165. Up-regulation in the presence of VEGF and TNF-α, but not LPS, IFN-γ, IL-4 and IL-17A, suggests a potential role for ALCAM in human retinal angiogenesis in some settings.

Differential Proinflammatory and Oxidative Stress Response and Vulnerability to Metabolic Syndrome in Habitual High-Fat Young Male Consumers Putatively Predisposed by Their Genetic Background

“…These factors included EGFL6 , Leptin , CTGF and cysteine-rich protein-61 ( CYR61 ) (Table S1). In addition, ALCAM [55] and CTSB [56] also involved in inflammatory processes had angiogenic activities.…”

Genetic polymorphisms of cell adhesion molecules in Behcet’s disease in a Chinese Han population

“…The role of CD6 and ALCAM in ocular inflammatory disease has not received much attention until now, although expression of ALCAM has been described for retinal vascular endothelial cells 48 . ALCAM expression on the retinal vascular endothelium is probably involved in neovascularization and not directly on the transmigration of inflammatory T cells into the retina 8 .…”

Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion through differential proteolysis

“…In the absence of evidence for an activation mechanism, such as phosphorylation, the regulation of ALCAM-mediated adhesion is thought to be achieved by controlling ALCAM binding availability. Regulation of ALCAM-ALCAM interactions can occur through changes in expression and membrane localization, proteolytic release of the ALCAM ectodomain, or antagonistic competition by this shed ectodomain and/or a soluble ALCAM isoform 9 , 10 , 17 , 25 . ALCAM, like many other Ig-CAMs, can be cleaved from the cell surface by the protease ADAM17, a process referred to as ectodomain shedding 9 , 26 .…”