Julianty Angsana1, Jiaxuan Chen1, Sumona Smith1, Jiantao Xiao1, Jing Wen1, Liying Liu1, Carolyn A Haller2, Elliot L Chaikof2. 1. From the Department of Bioengineering, Georgia Institute of Technology, Atlanta (J.A.); Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (J.C., L.L., C.A.H., E.L.C.); Department of Surgery, Emory University, Atlanta, GA (S.S., J.X., J.W.); and Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA (E.L.C.). 2. From the Department of Bioengineering, Georgia Institute of Technology, Atlanta (J.A.); Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (J.C., L.L., C.A.H., E.L.C.); Department of Surgery, Emory University, Atlanta, GA (S.S., J.X., J.W.); and Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA (E.L.C.). echaikof@bidmc.harvard.edu challer@bidmc.harvard.edu.
Abstract
OBJECTIVE: Syndecan-1 (Sdc-1) is a member of a family of cell surface proteoglycans, which has been reported to participate in the regulation of events relevant to tissue repair and chronic injury responses, including cell-substrate interactions, matrix remodeling, and cell migration. In this study, we report the functional significance of Sdc-1 in polarized macrophage populations and its role in adhesion and motility events relevant to resolution of the inflammatory program. APPROACH AND RESULTS: Macrophage Sdc-1 expression is associated with differentiated M2 macrophages with high intrinsic motility, and Sdc-1 deficiency is characterized by impaired migration and enhanced adhesion. Leukocyte infiltration and emigration were examined in a thioglycollate-induced model of peritonitis in Sdc-1(+/+) and Sdc-1(-/-) mice. Although the infiltration of inflammatory cells was similar in both cohorts, a significant delay in the lymphatic clearance of Sdc-1(-/-) macrophages was observed. Moreover, we observed enhanced inflammation and greater burden of atherosclerotic plaques in ApoE(-/-)Sdc-1(-/-) mice maintained on a Western diet. CONCLUSIONS: These results demonstrate that defective motility in Sdc-1(-/-) macrophages promotes a persistent inflammatory state with relevance to the pathogenesis of atherosclerosis.
OBJECTIVE:Syndecan-1 (Sdc-1) is a member of a family of cell surface proteoglycans, which has been reported to participate in the regulation of events relevant to tissue repair and chronic injury responses, including cell-substrate interactions, matrix remodeling, and cell migration. In this study, we report the functional significance of Sdc-1 in polarized macrophage populations and its role in adhesion and motility events relevant to resolution of the inflammatory program. APPROACH AND RESULTS: Macrophage Sdc-1 expression is associated with differentiated M2 macrophages with high intrinsic motility, and Sdc-1 deficiency is characterized by impaired migration and enhanced adhesion. Leukocyte infiltration and emigration were examined in a thioglycollate-induced model of peritonitis in Sdc-1(+/+) and Sdc-1(-/-) mice. Although the infiltration of inflammatory cells was similar in both cohorts, a significant delay in the lymphatic clearance of Sdc-1(-/-) macrophages was observed. Moreover, we observed enhanced inflammation and greater burden of atherosclerotic plaques in ApoE(-/-)Sdc-1(-/-) mice maintained on a Western diet. CONCLUSIONS: These results demonstrate that defective motility in Sdc-1(-/-) macrophages promotes a persistent inflammatory state with relevance to the pathogenesis of atherosclerosis.
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