Architectural remodelling in lungs of rabbits induced by type V collagen immunization: a preliminary morphologic model to study diffuse connective tissue diseases

Architectural remodelling in lungs of rabbits induced by type V collagen immunization: a preliminary morphologic model to study diffuse connective tissue diseases
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DOI:
10.1016/j.prp.2004.05.007
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发表时间:
2004-01-01
影响因子:
2.8
通讯作者:
Yoshinari, NH
Yoshinari, NH
中科院分区:
医学4区
文献类型:
--
作者:
Teodoro, WR;Velosa, AP;Yoshinari, NH

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弥漫性结缔组织病 (DCTD) 的发病机制仍不清楚,人们对其与细胞外基质 (ECM) 重塑相关的自身免疫方面进行了广泛研究,重点是炎症部位的胶原蛋白。本文描述了用人 V 型胶原蛋白免疫兔子后肺结构和修复/重塑对损伤的反应。动物模型由用与弗氏佐剂混合的胶原蛋白免疫的兔子组成,并在四剂抗原中的第一剂后7、15、30、75和120天处死。根据参考区室(实质和间质)和损伤,通过组织学、形态计量学和免疫荧光方法评估肺结构重塑反应: 1-炎症(多形核细胞和单核细胞); 2-修复(纤维化)和3-ECM重塑(胶原系统)。结果显示,肺血管和细支气管实质存在严重炎症,其特征是小动脉壁厚度增加、假性嗜酸性粒细胞和单核细胞浸润。肺ECM的渐进性重塑以间隔和支气管血管间质中的胶原沉积为特征,特别是在75天和120天处死的兔子中。当兔子接种 I 型和 III 型胶原蛋白时,ECM 重塑过程没有重现。我们得出的结论是,该模型再现了与许多 DCTD 中观察到的形态变化类似的形态变化,鼓励实现其他实验,以更好地了解这些疾病的发病机制。 (C) 2004 年爱思唯尔有限公司。版权所有。
The pathogenesis of diffuse connective tissue diseases (DCTD) is still unknown and has been extensively studied regarding its autoimmunity aspects related to extracellular matrix (ECM) remodelling, with an emphasis on the collagens at the inflammatory site. The present paper describes the pulmonary architectural and repair/remodelling responses to injury after immunization of rabbits with human type V collagen. The animal model consisted of rabbits immunized with collagen mixed with Freund's adjuvant and sacrificed 7, 15, 30, 75, and 120 days after the first of four doses of antigen. Pulmonary architecture remodelling response was evaluated by histology, morphometry, and the immunofluorescence method, according to compartments of reference (parenchyma and interstitium) and injury: 1-Inflammation (polymorphonuclear and mononuclear cells); 2-repair (fibrosis) and 3-ECM remodelling (collagen system). The results showed an intense inflammatory involvement of the pulmonary vascular and bronchiolar parenchyma, characterized by increased wall thickness in small arteries, infiltrations by pseudoeosinophils, and mononuclear cells. Progressive remodelling of the pulmonary ECM was characterized by collagen deposition in the septal and bronchovascular interstitium, especially In rabbits sacrifices at 75 and 120 days. The ECM remodelling process was not reproduced when rabbits were inoculated with collagen types I and III. We conclude that the model reproduces morphologic changes similar to those observed in many DCTD, encouraging realization of other experiments to gain a better understanding of the pathogenesis of these diseases. (C) 2004 Elsevier GmbH. All rights reserved.