Studies on activation and regulation of the coagulation cascade in chronic rhinosinusitis with nasal polyps - 04/08/22
, Bao-Feng Wang, MD, PhD b, c, James E. Norton, MS c, Lydia A. Suh, BS c, Roderick G. Carter, BS c, Whitney W. Stevens, MD, PhD c, Anna G. Staudacher, MS c, Julia H. Huang, MS d, Kathryn E. Hulse, PhD c, Anju T. Peters, MD c, d, Leslie C. Grammer, MD c, David B. Conley, MD d, Kevin C. Welch, MD d, Robert C. Kern, MD d, Zheng Liu, MD, PhD b, Jingying Ye, MD, PhD a, Robert P. Schleimer, PhD c, d, ⁎ Abstract |
Background |
Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP.
Objective |
We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS.
Methods |
Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin–antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting.
Results |
Increased levels of FXa, F1+2, and thrombin–antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue.
Conclusion |
The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.
Il testo completo di questo articolo è disponibile in PDF.Key words : Chronic rhinosinusitis, nasal polyps, CRSwNP, coagulation, FXa, prothrombin fragment 1+2, thrombin-anti-thrombin complex, tissue factor, FVII, tissue factor pathway inhibitor
Abbreviations used : AERD, COIP, CRS, CRSsNP, CRSwNP, ECP, F1+2, FVII, FVIIa, FX, FXa, IF, IHC, NP, PAR, TATc, TF, TFPI, UT
Mappa
| The first 2 authors contributed equally to this article, and both should be considered first author. |
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| Supported in part by National Institutes of Health grants (KL2 TR001424, K23 AI141694, R01 AI104733, U19 AI106683, and P01 145818), by National Natural Science Foundation of China grant 82171113 and 81800888, by Tongji Hospital Outstanding Youth grant 2016YQ04, by grants from the Parker B. Francis Fellowship Foundation and the American Partnership for Eosinophilic Disorders/American Academy of Allergy, Asthma & Immunology HOPE Pilot Grant Award, and by the Ernest S. Bazley Foundation. |
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| Disclosure of potential conflict of interest: W. W. Stevens served on an advisory board for GlaxoSmithKline. A. T. Peters reports personal fees from Sanofi Regeneron and personal fees and grants from AstraZeneca. L. C. Grammer reports personal fees from Astellas Pharmaceuticals. R. C. Kern reports personal fees from Sanofi, Novartis, Lyra Pharmaceutical, and Neurent. R. P. Schleimer reports consulting fees from Intersect ENT, Merck, GlaxoSmithKline, Sanofi, AstraZeneca/Medimmune, Genentech, Allakos, Actobio Therapeutics, Lyra Therapeutics, Astellas Pharma, and Otsuka Inc; and also receives royalties from Siglec-8– and Siglec-8 ligand–related patents licensed to Allakos. The authors declare that they have no relevant conflicts of interest. |
Vol 150 - N° 2
P. 467 - Agosto 2022 Ritorno al numero
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