Syndecan-1 modulates the motility and resolution responses of macrophages.

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.

• Authors: Julianty Angsana, Jiaxuan Chen, Sumona Smith, Jiantao Xiao, Jing Wen, Liying Liu, Carolyn A Haller, Elliot L Chaikof
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 35 Issue 2 Pg. 332-40 (Feb 2015) ISSN: 1524-4636 [Electronic] United States
• PMID: 25550207 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Apolipoproteins E
• Culture Media, Conditioned
• Sdc1 protein, mouse
• Syndecan-1

Topics

• Animals
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (genetics, immunology, metabolism, pathology)
• Cell Adhesion
• Cell Differentiation
• Cell Line, Tumor
• Chemotaxis
• Chemotaxis, Leukocyte
• Culture Media, Conditioned
• Diet, High-Fat
• Disease Models, Animal
• Humans
• Macrophages, Peritoneal (immunology, metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Phenotype
• Plaque, Atherosclerotic
• Signal Transduction
• Syndecan-1 (deficiency, genetics, metabolism)
• Time Factors