| First Author | Yakubenko VP | Year | 2011 |
| Journal | Circ Res | Volume | 108 |
| Issue | 5 | Pages | 544-54 |
| PubMed ID | 21252155 | Mgi Jnum | J:183492 |
| Mgi Id | MGI:5318817 | Doi | 10.1161/CIRCRESAHA.110.231803 |
| Citation | Yakubenko VP, et al. (2011) alphaMbeta(2) integrin activation prevents alternative activation of human and murine macrophages and impedes foam cell formation. Circ Res 108(5):544-54 |
| abstractText | RATIONALE: The alternative activation of monocytes by interleukin (IL)-13 and IL-4 is a significant component of the inflammatory response. The consequences of alternative activation in inflammatory diseases remain to be determined. OBJECTIVE: In this report, we explored how integrins, receptors important for monocyte migration to inflammatory sites, regulate IL-13-mediated monocyte activation. We focused on the analysis of 2 proteins, which are upregulated during the alternative activation and are important for the development of atherosclerosis, an oxidative enzyme 15-lipoxygenase (15-LO) and a scavenger receptor CD36. METHODS AND RESULTS: We found that adhesion of resting monocytes through beta(2) integrins and inside-out activation of beta(2) integrins by monocyte chemoattractant protein-1 did not change IL-13-stimulated 15-LO upregulation; however, preincubation of monocytes with the antibody MEM48, which generates full activation of beta(2) integrins, significantly inhibited 15-LO mRNA and protein expression. In contrast, activation of beta(1) integrins had no effect on 15-LO expression. Analysis of integrin clustering through alpha(M), alpha(L), alpha(X), and alpha(D) subunits demonstrated the pivotal role for integrin alpha(M)beta(2) in inhibiting 15-LO expression. IL-13 treatment upregulates 15-LO-dependent CD36 expression on human monocytes; our studies showed that beta(2) integrin activation and alpha(M) integrin clustering significantly inhibited IL-13-dependent CD36 mRNA and protein expression, as well as CD36-related foam cell formation. Moreover, IL-13 stimulation of alpha(M)-deficient peritoneal macrophages demonstrated an upregulated level of 15-LO induction, CD36 expression, and lipid accumulation as compared with wild-type controls. CONCLUSIONS: The adhesion of monocytes/macrophages through activated integrin alpha(M)beta(2) has a regulatory and potential atheroprotective function during the alternative activation of macrophages. |
