IMMUNIZATION WITH PSEUDOMONAS-AERUGINOSA VACCINES AND ADJUVANT CAN MODULATE THE TYPE OF INFLAMMATORY RESPONSE SUBSEQUENT TO INFECTION
IMMUNIZATION WITH PSEUDOMONAS-AERUGINOSA VACCINES AND ADJUVANT CAN MODULATE THE TYPE OF INFLAMMATORY RESPONSE SUBSEQUENT TO INFECTION
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DOI：
10.1128/iai.62.8.3146-3155.1994
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发表时间：
1994-08-01
影响因子：
3.1
通讯作者：
HOIBY, N
中科院分区：
文献类型：
--
作者：
JOHANSEN, HK;ESPERSEN, F;HOIBY, N
铜绿假单胞菌是囊性纤维化（CF）患者的主要病原体。为了研究通过疫苗预防肺部炎症和减缓感染进展的可能性，我们建立了慢性铜绿假单胞菌肺部感染的大鼠模型。用铜绿假单胞菌、全细胞超声、o -多糖毒素A缀合物、海藻酸盐-毒素A缀合物或天然海藻酸盐免疫大鼠。对照动物接受无菌生理盐水或不完全弗氏佐剂（IFA）。无菌生理盐水注射组的宏观（平均评分，2.4比2.7 ~ 3.2）和显微（平均评分，2.0比2.1 ~ 2.8）病理异常较免疫组和IFA组轻。在免疫大鼠中观察到的更严重的肺部异常可能是由于免疫复合物介导的肺组织损伤的结果。生理盐水对照大鼠的组织病理学结果显示，与CF患者一样，急性炎症以海藻酸珠（微菌落）周围的大量多形核白细胞为主。相比之下，IPA组和免疫大鼠的炎症反应由急性型炎症转变为以单核白细胞和散在肉芽肿为主的慢性炎症。两种海藻酸盐疫苗诱导产生交叉反应抗体，大多数免疫动物对同源抗原的免疫球蛋白M （IgM）、IgG和IgA类抗体滴度显著（P < 0.001）升高（酶联免疫吸附试验）。大多数免疫大鼠的细菌清除效率显著高于给予无菌生理盐水的对照组（P < 0.05）。目前的研究表明，没有一种疫苗可以在攻击后4周完全预防慢性肺部炎症。然而，免疫大鼠的病理状况改变为慢性炎症可能对CF患者的未来管理有很大的好处，因为发展中的肺组织损伤已被证明是由多形核白细胞释放的弹性酶引起的。
Pseudomonas aeruginosa is the predominant pathogen in patients with cystic fibrosis (CF). To study the possibility of preventing lung inflammation and decreasing the progression of the infection by vaccination, we have developed a rat model of chronic P. aeruginosa lung infection. Rats were immunized with P. aeruginosa ,whole-cell sonicates, O-polysaccharide toxin A conjugate, an alginate-toxin A conjugate, or native alginate. Control animals received sterile saline or incomplete Freund's adjuvant (IFA). The macroscopic (mean score, 2.4 versus 2.7 to 3.2) (P < 0.05) and microscopic (mean score, 2.0 versus 2.1 to 2.8) pathologic abnormalities were less severe in the control rats injected with sterile saline than in the immunized rats and the IFA group. The more severe lung abnormalities observed in Immunized rats could be due to the result of immune complex-mediated lung tissue damage. The histopathologic results in the saline control rats were characterized by acute inflammation dominated by numerous polymorphonuclear leukocytes surrounding the alginate beads (microcolonies), as in CF patients. In contrast, the inflammatory response in the IPA group and in the immunized rats had changed from an acute-type inflammation to a chronic-type inflammation dominated by mononuclear leukocytes and scattered granulomas. Cross-reacting antibodies were induced by the two alginate vaccines, and most immunized animals developed a significant (P < 0.001) antibody titer elevation (in enzyme-linked immunosorbent assay) of the immunoglobulin M (IgM), IgG, and IgA classes against the homologous antigens. The bacterial clearance was significantly (P < 0.05) more efficient in most immunized rats than in the control rats given sterile saline. The present study shows that none of the vaccines could Completely prevent chronic lung inflammation 4 weeks after challenge. However, the changed pathologic condition in immunized rats to a chronic-type inflammation might be of great benefit in future management of CF patients since the developing lung tissue damage has been shown to be caused by polymorphonuclear leukocyte-released elastase.