Abstract
Airway inflammation is associated with increased permeability and leakage of plasma coagulation factors, leading to activation of the coagulation system in the extravascular space. We reported that significant concentrations of thrombin and thrombin-antithrombin complex were found in nasal secretion from patients with chronic rhinosinusitis. Thrombin and PAR-1 agonist peptide stimulated secretion of PDGF, VEGF and mucus (MUC5AC) from cultured airway epithelial cells. We also found higher expressions of PDGF, VEGF and their receptors in nasal polyps from patients with chronic rhinosinusitis, suggesting that thrombin-induced PDGF and VEGF may be involved in the formation of nasal polyps. Intranasal instillation with thrombin induced goblet cell metaplasia and mucus production in rat nasal epithelium in vivo. These results indicate that the activation of coagulation system occurs during the sinonasal inflammation and that thrombin plays a crucial role in tissue remodeling such as goblet cell metaplasia and formation of nasal polys.
Activated protein C (APC) and heparin are anticoagulant drugs in clinical practice and both have anti-inflammatory activities. Heparin plays regulatory roles in inflammation and subsequent tissue remodeling by binding nonspecifically to many proteins involved in the inflammatory process, including cytokines, growth factors, adhesion molecules and tissue-destructive enzymes. We reported that heparin inhibited TNF-α-induced secretion of mucus (MUC5AC) and IL-8 from cultured airway epithelial cells, and that intranasal instillation with heparin attenuated LPS-induced goblet cell metaplasia and neutrophil infiltration in rat nasal epithelium. Nasal administration with anticoagulant drugs, APC and heparin may provide a new therapeutic strategy for the treatment of chronic rhinosinusitis.
