Cell-surface glycosaminoglycans (GAGs)

Cell-surface glycosaminoglycans (GAGs) are complex, linear polysaccharides found on the surface of respiratory epithelial cells, primarily as part of proteoglycans like syndecans and glypicans (Clausen et al., 2020, Cell). These molecules, particularly heparan sulfate, serve as critical attachment factors for numerous respiratory pathogens, including SARS-CoV-2, influenza, and Pseudomonas aeruginosa, by facilitating initial docking and concentrating microbes near their high-affinity entry receptors (Aquino & Park, 2016, "Glycosaminoglycans: Sweet Determinants of Bacterial Pathogenesis"). Beyond their role in infection, GAGs are essential regulators of the pulmonary microenvironment, where they sequester chemokines and growth factors to modulate inflammatory responses and tissue repair (Gaggar & Weathington, 2016, "Bioactive Glycosaminoglycans in Airway Disease"). In chronic respiratory diseases such as COPD and cystic fibrosis, the composition and integrity of the GAG layer are often altered, contributing to persistent inflammation and increased susceptibility to infection. Therapeutic strategies targeting GAGs include the use of soluble GAG mimetics to competitively inhibit pathogen binding or heparanase inhibitors to prevent the degradation of the protective epithelial glycocalyx (O'uo et al., 2021, "Heparanase: A potential therapeutic target in COVID-19"). However, drug development must address challenges such as the potential for systemic anticoagulation and the disruption of homeostatic signaling pathways mediated by these versatile carbohydrates.

Other names

Heparan sulfateChondroitin sulfateDermatan sulfateKeratan sulfateCell-surface proteoglycansHeparan sulfate proteoglycans (HSPGs)

Competitive inhibition of pathogen binding to host cells, modulation of inflammatory cytokine activity, and inhibition of heparanase-mediated degradation of the glycocalyx.