Syndecan-1 Modulates the Motility and Resolution Responses of Macrophages
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.
- Received November 18, 2013.
- Accepted December 14, 2014.
- © 2014 American Heart Association, Inc.