S A T U R D A Y 210 Excessive Fibrin Deposition Caused by a Fibrinolytic Disorder Associated with Reduction of Tissue Plaminogen Activator Expression in Nasal Polyps Tetsuji Takabayashi, MD, Atsushi Kato, PhD, Anju Peters, MD, Kathryn E. Hulse, PhD, Lydia Suh, BSc, Roderick Carter, BSc, James Norton, MS, Leslie C. Grammer, MD, FAAAAI, Seong Ho Cho, MD, Bruce Tan, MD, Rakesh Chandra, MD, David Conley, MD, Robert Kern, MD, Shigeharu Fujieda, MD, Robert P. Schleimer, PhD, FAAAAI; Northwestern University Feinberg School Medicine, Chicago, IL, Northwestern University Feinberg School of Medicine, Chicago, IL, Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, Northwestern University Feinberg School of Medicine, Chicago, IL, University of Fukui, Fukui, Japan. RATIONALE: Nasal polyps (NP) are characterized by intense edema or pseudocyst formation with a high content of plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in submucosa remain unclear. We hypothesized that formation of fibrin mesh retains plasma proteins in NP.We assessed the fibrin deposition and expression of the fibrinolytic components in patients with chronic rhinosinusitis (CRS). METHODS: We collected nasal tissue from patients with CRS and control subjects. We assessed fibrin deposition by means of immunofluorescence. Fibrinolytic components, d-dimer and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in primary airway epithelial cells. RESULTS: Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from CRS and control subjects (6.6 fold increase, p<.001). Levels of the cross-linked fibrin cleavage product d-dimer were significantly decreased in NP compared with UT from CRS and control, suggesting reduced fibrinolysis (4.3 fold, p<.01). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from CRS and control (P < .001). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Additionally, plasminogen activator protein levels in UT were lower than inferior turbinate tissue from both CRS and control. Th2 cytokine stimulated cultured airway epithelial cells showed downregulation of t-PA. CONCLUSIONS: A reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, possibly contributing to the tissue remodeling and pathogenesis of CRSwNP.