Inflammation and infection in naive human cystic fibrosis airway grafts
Inflammation and infection in naive human cystic fibrosis airway grafts
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DOI：
10.1165/ajrcmb.23.2.4214
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发表时间：
2000-08-01
影响因子：
6.4
通讯作者：
Puchelle, E
中科院分区：
文献类型：
--
作者：
Tirouvanziam, R;de Bentzmann, S;Puchelle, E
炎症加剧现在被认为是囊性纤维化（CF）气道疾病的重要组成部分。炎症是CF基本缺陷的一部分还是对持续性感染的反应仍有争议。我们在严重联合免疫缺陷小鼠中使用人类胎儿气管移植物来解决这个问题。该模型产生组织学上成熟的，最重要的是，幼稚CF和非CF替代气道。在幼稚CF气道移植物中发现明显的炎症不平衡，包括腔内白细胞介素8含量高度增加（CF: 10.1 +/- 2.2 ng/ml；非CF: 1.2 +/- 0.6 ng/ml; P < 0.05）和白细胞在上皮下区域的一致积累（P < 0.001）。CF气道移植物在组织学上没有受到影响，直到铜绿假单胞菌攻击，它引起：(1)早期（3小时前）大量白细胞经上皮迁移，(2)强烈的上皮脱落，(3)细菌向固有层快速进展。在非CF移植物中，这三组事件在6小时前没有观察到。使用一个幼稚的人类气道模型，因此我们证明在任何感染之前，CF气道处于促炎状态。感染后，基底炎症失衡对粘膜造成严重损害，为细菌定植和CF气道疾病的后续步骤铺平了道路。
Exacerbated inflammation is now recognized as an important component of cystic fibrosis (CF) airway disease. Whether inflammation is part of the basic defect in CF or a response to persistent infection remains controversial. We addressed this question using human fetal tracheal grafts in severe combined immunodeficient mice. This model yields histologically mature, and most importantly, naive CF and non-CF surrogate airways, Significant inflammatory imbalance was found in naive CF airway grafts, including a highly increased intraluminal interleukin 8 content (CF: 10.1 +/- 2.2 ng/ml; non-CF: 1.2 +/- 0.6 ng/ml; P < 0.05) and consistent accumulation of leukocytes in the subepithelial region (P < 0.001). CF airway grafts were not histologically affected until challenged with Pseudomonas aeruginosa, which provoked: (1) early (before 3 h) and massive leukocyte transepithelial migration, (2) intense epithelial exfoliation, and (3) rapid progression of bacteria toward the lamina propria, In non-CF grafts, these three sets of events were not observed before 6 h. Using a model of naive human airways, we thus demonstrate that before any infection, CF airways are in a proinflammatory state. After infection, the basal inflammatory imbalance contributes to exert severe damage to the mucosa, paving the way for bacterial colonization and subsequent steps of CF airway disease.