Soy Isoflavones Attenuate Human Monocyte Adhesion to Endothelial Cell–Specific CD54 by Inhibiting Monocyte CD11a

Abstract

Soy-based diets have been shown to protect against the development of atherosclerosis; however, the underlying mechanism(s) remain unknown. Interaction between activated monocytes and inflamed endothelial cells is an early event in atherogenesis. Therefore, we examined whether treatment of monocytes with soy phytochemicals could inhibit their adhesion to the endothelial cell-specific protein, CD54, a key factor in monocyte adhesion. Female Sprague-Dawley rats were fed AIN-93G diets containing soy protein isolate or casein. Sera from soy-fed rats inhibited CD54-dependent monocyte adhesion, whereas sera from casein-fed rats did not. To determine whether isoflavones in the sera of soy-fed rats were involved in this inhibition, monocytes were preincubated with soy isoflavones. Isoflavone treatment inhibited monocyte adhesion to CD54 protein, as well as to endothelial cells expressing CD54. Monocyte expression of CD11a, the cognate receptor for CD54, was unaffected by isoflavones. However, binding of the activation epitope-specific antibody mAb24, which binds specifically to the active form of CD11a, was significantly lower in soy isoflavone-treated monocytes than in media-treated cells. These findings suggest that inhibition of CD54-dependent monocyte adhesion by soy isoflavones is mediated in part by affinity regulation of CD11a. Inhibition of monocyte adhesion to endothelial cells by isoflavones resulted in reduced expression of the inflammatory cytokines IL-6 and IL-8. Collectively, these data suggest that the athero-protective effect of soy diets may be mediated by blocking monocyte-endothelial cell interaction.

Mechanisms of anti-atherosclerotic functions of soy-based diets

“…Interestingly, soy-based diet inhibits the expression of MCP-1 in the aorta [22], and this observation is also supported by the reduced number of macrophages in atherosclerotic lesion in mice fed soy-based diets compared to control casein diet [22]. Moreover, coculture of human monocytes with endothelial cells resulted in the increased secretion of pro-inflammatory cytokines, such as IL-6 and IL-8, and the addition of soy isoflavones to the monocyte/endothelial cell co-culture inhibited the secretion of these pro-inflammatory cytokines [53]. However, plasma MCP-1 levels were not different in mice fed soy or control (casein) diet [22].…”

“…Activation of monocytes and T lymphocytes results in the transformation of CD11a from a lowaffinity or avidity to a high-affinity or avidity form [56,57], and such a transformation leads to firm adhesion of inflammatory cells to vascular endothelium through CD11a-CD54 interaction. Recent in vitro studies have shown that pre-exposure of monocytes to soy isoflavones (1 μM) inhibited oxLDL-induced monocyte adhesion to endothelial cells [53]. However, this inhibition of monocyte adhesion is not due to the change in CD11a expression.…”

“…In vitro studies using human monocytic cell lines showed that oxLDL treatment of monocytic cells increases their adhesion to endothelial cells [53]. Furthermore, pre-exposure of monocytes to soy isoflavones (1 μM final concentration with equimolar mixture of genistein, daidzein and equol) as well as to sera from animals fed soy diet inhibited oxLDLinduced monocyte adhesion to endothelial cells [53]. These studies suggest that there is a direct effect of soy isoflavones on monocyte activation and subsequent adhesion, although the detailed mechanism is not known.…”

Immunomodulatory bioactivity of soy and milk ferments on monocyte and macrophage models

“…In addition, milk and soy both contain estrogen-like components which may interact with estrogen receptors on monocytes and macrophages, influencing cellular responses (Purup, Vestergaard, Pederson, & Sejrsen 2006).The decrease in CD54 expression may prevent both monocyte stage and macrophage stage cells from adhering efficiently to endothelial cells (Maio & Del Vecchio 1992), impeding cell travel to the site of infection and therefore limiting the pro-inflammatory response. For soy treated cells, the soy isoflavone genistein may play a role in inhibiting monocyte adhesion (Nagarajan, Stewart, & Badger 2006) which could explain why even unfermented and acidified soy controls down-regulate CD54 expression to the same extent as that observed with soy ferments.…”

Administration of β-glycolipids overcomes an unfavorable nutritional dependent host milieu: a role for a soy-free diet and natural ligands in intrahepatic CD8+ lymphocyte trapping and NKT cell redistribution

“…Interactions between activated monocytes and inflamed endothelial cells are an early event in atherogenesis. Treatment of monocytes with soy phytochemicals inhibited their adhesion to the endothelial cell-specific protein, CD54, a key factor in monocyte adhesion [10].…”