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Inflammation‐Induced Syndecan Shedding Contributes to Endothelial Barrier Dysfunction
Author(s) -
Jannaway Melanie,
Yang Xiaoyuan,
Meegan Jamie E,
Yuan Sarah Y
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.834.7
Subject(s) - syndecan 1 , glycocalyx , ectodomain , microbiology and biotechnology , proteases , matrix metalloproteinase , lipopolysaccharide , barrier function , metalloproteinase , disintegrin , inflammation , glycosaminoglycan , endothelial stem cell , chemistry , immunology , biology , cell , biochemistry , in vitro , receptor , enzyme
The endothelial glycocalyx (GCX) is a complex matrix of glycosaminoglycans and proteoglycans such as syndecans (SDCs), which form a protective layer on the vascular luminal surface contributing to the endothelial barrier function. Ectodomain shedding of transmembrane proteoglycans or degradation of GCX components can damage barrier integrity. The objective of this study was to investigate the involvement of a disintegrin and metalloproteinase 15 (ADAM15) in GCX shedding, and the effects of SDC fragments on endothelial barrier function. A confocal microscopic imaging analysis of mouse lungs demonstrated reduced SDC expression on microvascular endothelial surface following lipopolysaccharide (LPS) treatment, an effect blunted in ADAM15−/− mice, implicating ADAM15 in GCX injury. ELISA analysis of human lung perfusate collected following LPS perfusion showed increased soluble SDC concentration, indicating LPS‐induced SDC shedding. Furthermore, when analyzed via transmission electron microscopy, microvessels within these LPS‐perfused samples displayed evidence of GCX injury. Together, these results suggest that an inflammatory state can lead to the shedding of endothelial SDCs, likely through the activities of proteases and sheddases including ADAM15.