Objective
Syndecan-1 (Sdc-1) is a member of a family of cell surface proteoglycans that 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 their 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 plaque 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.