期刊
MOLECULES
卷 26, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/molecules26185512
关键词
glycosaminoglycans; heparan sulfate; lung; disaccharide composition; chemokines; chemokine; GAG interactions
This study isolated and characterized heparan sulfate from human lung tissues, identifying syndecans as the predominant proteoglycan class in human lungs. The disaccharide composition was found to vary among individuals according to sex, age, and health stage. Differences in the composition affected the binding affinities of chemokines, suggesting selective immune cell responses depending on the relative chemokine-glycan affinities. This provides important new insights for potentially developing individualized therapies for lung immunological disorders targeting HS.
Glycosaminoglycans are a class of linear, highly negatively charged, O-linked polysaccharides that are involved in many (patho)physiological processes. In vitro experimental investigations of such processes typically involve porcine-derived heparan sulfate (HS). Structural information about human, particularly organ-specific heparan sulfate, and how it compares with HS from other organisms, is very limited. In this study, heparan sulfate was isolated from human lung tissues derived from five donors and was characterized for their overall size distribution and disaccharide composition. The expression profiles of proteoglycans and HS-modifying enzymes was quantified in order to identify the major core proteins for HS. In addition, the binding affinities of human HS to two chemokines-CXCL8 and CCL2-were investigated, which represent important inflammatory mediators in lung pathologies. Our data revealed that syndecans are the predominant proteoglycan class in human lungs and that the disaccharide composition varies among individuals according to sex, age, and health stage (one of the donor lungs was accidentally discovered to contain a solid tumor). The compositional difference of the five human lung HS preparations affected chemokine binding affinities to various degrees, indicating selective immune cell responses depending on the relative chemokine-glycan affinities. This represents important new insights that could be translated into novel therapeutic concepts for individually treating lung immunological disorders via HS targets.
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