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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #187189
Title: SOY ISOFLAVONES ATTENUATE HUMAN MONOCYTE ADHESION TO ENDOTHELIAL CELL-SPECIFIC CD54 BY INHIBITING MONOCYTE CD11A1

Author
item NAGARAJAN, SHANMUGAM - ACNC/UAMS
item STEWART, BRADFORD - ACNC
item BADGER, THOMAS - ACNC/UAMS

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2006
Publication Date: 7/11/2006
Citation: Nagarajan, S., Stewart, B.W., Badger, T.M. 2006. Soy isoflavones attenuate human monocyte adhesion to endothelial cell-specific CD54 by inhibiting monocyte cd11a1. Journal of Nutrition. 136(9):1-7.

Interpretive Summary: Heart attack is caused by reduced blood flow to the heart. This is due to the thickening of blood vessels. Recent studies have shown that soy diets prevent thickening of blood vessels. But we do not know how soy diet does this. Thickening of blood vessels is due to the attachment of blood cells to blood vessels. The attachment is controlled by a group of proteins called cell adhesion molecules. We studied whether the phytochemicals present in soy diet block the contact between these cells. The results from this study suggest that dietary soy protects the thickening of blood vessels by blocking blood cell and blood vessel cell contact. This may have important implications for people who consumed soy formula as infants.

Technical Abstract: Soy-based diets have been shown to protect against development of atherosclerosis, however, the mechanism(s) underlying these effects are not completely clear. Since, interaction of activated-monocytes to inflamed-endothelial cells is an early event in the atherogenesis, we hypothesized that phytochemicals associated with soy protein could inhibit the interaction between these cells. This hypothesis was addressed by determining the adhesion of soy phytochemicals-treated monocytes to endothelial cell specific molecule, CD54, a key player in monocyte adhesion. Adhesion assays showed un-activated human monocytic cell line (U937 cells) did not adhere to CD54, while oxidized-low density lipoprotein (oxLDL) or PMA treatment resulted in its adhesion to CD54, suggesting activation of monocytes is a prerequisite for its adhesion to CD54. Sera from soy diet-fed rats (soy-sera) inhibited the CD54-dependent monocyte adhesion, while this effect was not observed using sera from casein-fed rats. To determine whether the isoflavone component of soy-sera played a role in this inhibition, monocytes were preincubated with soy isoflavones and found to inhibit PMA or oxLDL-induced adhesion to CD54. Similar findings were also observed with endothelial cells expressing CD54. Further, inhibition of monocyte adhesion to endothelial cells by isoflavones resulted in reduced expression of inflammatory cytokines, IL-6 and IL-8. Expression of CD11a (the cognate receptor for CD54) on monocytes was found to be unaffected by isoflavones indicating that the inhibition of CD54-dependent monocyte adhesion by isoflavone is not due to the down regulation of CD11a expression. However, binding of activation-epitope specific antibody mAb24, which specifically binds to active form of CD11a, was significantly reduced in soy isoflavone-treated monocytes compared to 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. Collectively, these data suggest that athero-protective effect of soy diets could be mediated by blocking monocyte-endothelial cell interactions.