Open veterinary journal · 2026
Glycocalyx disruption mediates HP-PRRSV-induced microvascular endothelial dysfunction and underlies astragalus polysaccharide's antiviral efficacy.
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Xia Nuohan, Sun Jian, Hu Ge, Zhang Qian, Zhang Tao
Аннотация
BACKGROUND: Pulmonary microvascular endothelial cells (MVECs) are not only targets of the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) but also the pivotal hub of inflammation, interacting with alveolar macrophages to amplify the inflammatory response and determine the extent of tissue damage. Glycocalyx disruption in MVECs is often the initiating factor of numerous functional disorders, and astragalus polysaccharide (APS) has been shown to improve glycocalyx integrity in MVECs.
AIM: This study aimed to investigate the mediating role of glycocalyx disruption in HP-PRRSV-induced pulmonary microvascular endothelial dysfunction and the glycocalyx contribution to the anti-HP-PRRSV efficacy of APS.
METHODS: In vitro porcine pulmonary MVECs were infected with the HP-PRRSV JXA1 strain and treated with APS with or without prior glycocalyx degradation mediated by heparinase (HPA) III. The expression of glycocalyx components, PRRSV N protein, and adhesion molecules was detected using western blotting or flow cytometry. The barrier function was analyzed by measuring trans-endothelial electric resistance (TEER) and permeability of horseradish peroxidase-labeled streptavidin (HRP-SA). Furthermore, neutrophil TEM and its bactericidal capacity were assayed using Transwell plates.
RESULTS: HP-PRRSV infection reduced the expression of heparan sulfate proteoglycan 2 (HSPG-2), glypican-1, and syndecan-1 proteoglycans. It also lowered labeled Lens culinaris agglutinin, Datura stramonium agglutinin, and Phaseolus vulgaris agglutinin-E -reactive glycan ligand levels in porcine pulmonary MVECs. However, APS significantly alleviated this damage. Furthermore, its infection decreased TEER, increased HRP-SA permeability, elevated vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, promoted neutrophil TEM, and impaired their bactericidal activity. APS markedly suppressed HP-PRRSV replication and restored these virus-induced impairments. Conversely, enzymatic glycocalyx removal with HPA III intensified microvascular endothelial injury and largely weakened the APS's restorative effect.
CONCLUSION: Glycocalyx disruption is a critical pathogenic event that orchestrates pulmonary microvascular endothelial dysfunction during HP-PRRSV infection. More importantly, we delineated a novel mechanism by which APS exerts its therapeutic effects.
AIM: This study aimed to investigate the mediating role of glycocalyx disruption in HP-PRRSV-induced pulmonary microvascular endothelial dysfunction and the glycocalyx contribution to the anti-HP-PRRSV efficacy of APS.
METHODS: In vitro porcine pulmonary MVECs were infected with the HP-PRRSV JXA1 strain and treated with APS with or without prior glycocalyx degradation mediated by heparinase (HPA) III. The expression of glycocalyx components, PRRSV N protein, and adhesion molecules was detected using western blotting or flow cytometry. The barrier function was analyzed by measuring trans-endothelial electric resistance (TEER) and permeability of horseradish peroxidase-labeled streptavidin (HRP-SA). Furthermore, neutrophil TEM and its bactericidal capacity were assayed using Transwell plates.
RESULTS: HP-PRRSV infection reduced the expression of heparan sulfate proteoglycan 2 (HSPG-2), glypican-1, and syndecan-1 proteoglycans. It also lowered labeled Lens culinaris agglutinin, Datura stramonium agglutinin, and Phaseolus vulgaris agglutinin-E -reactive glycan ligand levels in porcine pulmonary MVECs. However, APS significantly alleviated this damage. Furthermore, its infection decreased TEER, increased HRP-SA permeability, elevated vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, promoted neutrophil TEM, and impaired their bactericidal activity. APS markedly suppressed HP-PRRSV replication and restored these virus-induced impairments. Conversely, enzymatic glycocalyx removal with HPA III intensified microvascular endothelial injury and largely weakened the APS's restorative effect.
CONCLUSION: Glycocalyx disruption is a critical pathogenic event that orchestrates pulmonary microvascular endothelial dysfunction during HP-PRRSV infection. More importantly, we delineated a novel mechanism by which APS exerts its therapeutic effects.