Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps.
Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps.
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DOI：
10.1016/j.jaci.2013.02.003
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发表时间：
2013-09
影响因子：
14.2
通讯作者：
Schleimer, Robert P.
中科院分区：
文献类型：
--
作者：
Takabayashi, Tetsuji;Kato, Atsushi;Peters, Anju T.;Hulse, Kathryn E.;Suh, Lydia A.;Carter, Roderick;Norton, James;Grammer, Leslie C.;Tan, Bruce K.;Chandra, Rakesh K.;Conley, David B.;Kern, Robert C.;Fujieda, Shigeharu;Schleimer, Robert P.
关键词：
严重水肿或形成含有血浆蛋白的假性囊肿是鼻息肉（NP）的突出特征。然而，粘膜下层血浆蛋白的NP保留的机制仍不清楚。最近，我们报道了纤维蛋白溶解障碍导致NP中纤维蛋白沉积过多，这可能与血浆蛋白的滞留有关。虽然凝血级联反应在血管外部位纤维蛋白凝块形成中起关键作用，但NP中凝血因子的表达和作用仍不清楚。本研究旨在探讨慢性鼻窦炎（CRS）患者凝血因子的表达。从CRS患者和对照受试者中收集鼻窦组织。采用实时荧光定量PCR法检测FXIII-A mRNA的表达，ELISA法、免疫组化法和免疫荧光法检测FXIII-A蛋白的表达。与CRS患者或对照受试者的钩突组织相比，CRS伴鼻息肉患者的NP中FXIII-A mRNA水平显著升高（CRSwNP; P <0.001）。类似地，NP中FXIII-A蛋白水平增加。免疫荧光分析显示炎症细胞中有FXIII-A表达，NP中FXIII-A+细胞数量显著增加。在NP中的CD68 +/CD163 + M2巨噬细胞内观察到大多数FXIII-A染色。FXIII-A的水平与M2巨噬细胞的标志物相关，表明M2巨噬细胞是NP中主要的FXIIIA产生细胞。M2巨噬细胞过量产生FXIII-A可能导致NP粘膜下层纤维蛋白过度沉积，这可能有助于组织重塑和CRSwNP的发病机制。
Profound edema or formation of a pseudocyst containing plasma proteins is a prominent characteristic of Nasal polyps (NP). However, the mechanisms underlying NP retention of plasma proteins in the submucosa remain unclear. Recently, we reported that impairment of fibrinolysis causes excessive fibrin deposition in NP and this might be involved in retention of plasma proteins. Although the coagulation cascade plays a critical role in fibrin clot formation at extravascular sites, the expression and role of coagulation factors in NP remain unclear. The objective of this study was to investigate the expression of coagulation factors in patients with chronic rhinosinusitis (CRS). Sinonasal tissues were collected from patients with CRS and control subjects. We assayed mRNA for factor XIII-A (FXIII-A) by using real-time PCR and measured FXIII-A protein by means of ELISA, immunohistochemistry and immunofluorescence. FXIII-A mRNA levels were significantly increased in NP from patients with CRS with nasal polyps (CRSwNP; P < .001) compared with uncinate tissue from patients with CRS or control subjects. Similarly, FXIII-A protein levels were increased in NP. Immunofluorescence analysis revealed FXIII-A expression in inflammatory cells, and FXIII-A+ cell numbers were significantly increased in NP. Most FXIII-A staining was observed within CD68+/CD163+ M2 macrophages in NP. Levels of FXIII-A correlated with markers of M2 macrophages, suggesting that M2 macrophages are major FXIIIA producing cells in NP. Overproduction of FXIII-A by M2 macrophages might contribute to the excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRSwNP.
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DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.0801375
发表时间：
2009-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kato A;Chustz RT;Ogasawara T;Kulka M;Saito H;Schleimer RP;Matsumoto K
通讯作者：
Matsumoto K
影响因子：
24.3
作者：
Hanf, G;Noga, O;Kunkel, G
通讯作者：
Kunkel, G
影响因子：
2.2
作者：
Katona, É;Ajzner, É;Muszbek, L
通讯作者：
Muszbek, L
DOI：
10.1161/01.atv.0000081636.25235.c6
发表时间：
2003-08-01
影响因子：
8.7
作者：
Dardik, R;Solomon, A;Inbal, A
通讯作者：
Inbal, A