VACCINATION PROMOTES TH1-LIKE INFLAMMATION AND SURVIVAL IN CHRONIC PSEUDOMONAS-AERUGINOSA PNEUMONIA IN RATS
VACCINATION PROMOTES TH1-LIKE INFLAMMATION AND SURVIVAL IN CHRONIC PSEUDOMONAS-AERUGINOSA PNEUMONIA IN RATS
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DOI：
10.1164/ajrccm.152.4.7551392
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发表时间：
1995-10-01
影响因子：
24.7
通讯作者：
HOIBY, N
中科院分区：
文献类型：
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作者：
JOHANSEN, HK;HOUGEN, HP;HOIBY, N
在模拟囊性纤维化（CF）的慢性铜绿假单胞菌肺部感染的大鼠模型中，我们研究了接种疫苗是否可以改变炎症反应。用解聚的藻酸盐毒素A缀合物（D-ALG毒素A）、纯化的藻酸盐、O-多糖毒素A缀合物或无菌盐水免疫大鼠。在攻击后，用D-ALG毒素A免疫的大鼠无一死亡，与其他两个疫苗组组合相反（p = 0.03）。与其他三组相比，在用D-ALG毒素A免疫的大鼠中观察到肉眼可见的肺部炎症严重程度的显著降低（p = 0.009）。对照组大鼠的组织病理学反应主要由藻酸盐珠周围的许多多形核白细胞（PMN）。与此相反，D-ALG毒素A免疫的大鼠的组织病理学反应在第一周内从主要的中性粒细胞（TH 2样）的挑战，以慢性型炎症为主的单核白细胞（TH 1样）。因此，D-ALG毒素A疫苗诱导的抗体滴度在攻击后与对照大鼠的抗体滴度没有差异。这项研究确定了一种可能的新方法，修改炎症，从而防止中性粒细胞介导的肺组织损伤在慢性铜绿假单胞菌肺部感染的CF。
In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from predominantly PMNs (TH2-like) to a chronic-type inflammation dominated by mononuclear leukocytes (TH1-like). In accordance, the antibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying the inflammation and thereby preventing the PMN-mediated lung tissue damage during chronic P. aeruginosa lung infection in CF.