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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #195546
Title: SOY ISOFLAVONES INHIBIT LEUKOCYTE INTEGRIN, CD11A-DEPENDENT MONOCYTE ADHESION TO ENDOTHELIAL CELLS

Author
item NAGARAJAN, SHANMUGAM - ACNC/UAMS
item STEWART, BRAD - ACNC
item FERGUSON, MATTHEW - ACNC
item BADGER, THOMAS - ACNC/UAMS

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/6/2006
Publication Date: 3/27/2006
Citation: Nagarajan, S., Stewart, B.W., Ferguson, M.E., Badger, T.M. 2006. Soy isoflavones inhibit leukocyte integrin, CD11a-dependent monocyte adhesion to endothelial cells. The FASEB Journal. 20(4):A124.

Interpretive Summary: Thickening of arteries is called atherosclerosis and this causes heart attack. Eating soybean diets has been shown to prevent atherosclerosis, but the mechanisms of this prevention are not known. Contact between endothelial cells (lining the blood vessels) and monocyte is essential for the start of atherosclerosis. We studied whether soybean diet can inhibit the contact between these two cells. We showed that soybean diets inhibit the contact between these cells. Based on these findings we feel soybean diets prevent atherosclerosis by blocking the cell-cell contact. We will extend these studies to learn how early exposure to soy diets alter these effects.

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 between endothelial cells and monocytes 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 phytochemcials treated monocytes to endothelial cell specific molecule, CD54, an important player in monocyte adhesion. Adhesion assays showed unactivated U937 cells did not adhere to CD54-coated plates, while oxLDL or PMA treatment resulted in its adhesion to CD54, suggesting activation is a prerequisite for monocyte adhesion. Sera from soy diet-fed rats inhibited the CD54-dependent monocyte adhesion (p<0.001), while this effect was not observed using sera from casein-fed animals. To determine whether the isoflavone component of soy diet played a role in this inhibition, monocytes were preincubated with soy isoflavones and found to inhibit (P<0.05) 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 and release of IL-6 and IL-8. To determine the mechanism(s) by which soy isoflavone inhibits monocyte adhesion to CD54, expression of CD11a (cognate ligand for CD54) was determined in monocytes. Expression of CD11a 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, the binding of activation-epitope specific antibody mAb24, which specifically binds to activated-epitope 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 studies suggest that athero-protective effect of soy could be mediated by blocking the monocyte and endothelial cell interaction by soy protein bound isoflavones.