Abstract 558: A Role for Syndecan-1 in the Motility of Alternatively Activated Macrophages
Background 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 and proliferation. We have previously demonstrated that macrophage Sdc-1 expression is up-regulated and protective in 2 clinically relevant models of chronic inflammation: elastase-induced AAA and Western diet-induced atherosclerosis. In this study, we aim to define the subtype and functional consequence of Sdc-1 expressing macrophages.
Methods Human and mouse Sdc-1 macrophages were enriched and characterized against defined macrophage subtypes, including classically activated M1(IFN-γ/LPS), M2 (IL-4), and M2 (IL-10). Endpoints included (i) surface expression of MHCII, CD86, PD-L2, and Sdc-1; (ii) iNOS and arginase activity; and (iii) ELISA or qPCR cytokine and chemokine analysis. Motility was examined using boyden chamber chemotaxis and adhesion to ECM was measured using CSFE labeled macrophages.
Results In vitro characterization of Sdc-1 expressing macrophages, which can be generated through the activation of cAMP/PKA signaling pathway or through exposure to adenosine, indicates that Sdc-1 expression defines an anti-inflammatory population with high intrinsic motility. Sdc-1 macrophages displayed reduced expression of pro-inflammatory cytokines and chemokines and displayed limited potential to mediate monocyte or CD4 T cell chemotaxis. Using Sdc-1-/- macrophages, we found that the absence of Sdc-1 is associated with defective actin reorganization, resulting in dampened macrophage migration and enhanced adhesion to extracellular matrix. Analysis with human macrophages confirmed Sdc-1 expression in an alternatively activated, motile population.
Conclusions Collectively, these results reinforce the physiological significance of macrophage motility as an endogenous modulator of the inflammatory response and further suggest Sdc-1 as a marker of alternatively activated macrophages in chronic inflammation.
- © 2013 by American Heart Association, Inc.