Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P-gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice
Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P-gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice
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DOI：
10.1128/iai.01572-07
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发表时间：
2008-07-01
影响因子：
3.1
通讯作者：
Yamamoto, M.
中科院分区：
文献类型：
--
作者：
Koizumi, Y.;Kurita-Ochiai, T.;Yamamoto, M.
牙龈卟啉单胞菌已被证明可以加速高脂血症动物动脉粥样硬化病变的发展。我们评估了抗牙龈假单胞菌感染的鼻用疫苗预防动脉粥样硬化的潜力。采用40 kda的牙龈假单胞菌外膜蛋白（OMP）加霍乱毒素（CT）作为佐剂，经鼻免疫自发性高脂血症（Apoe(shl)）小鼠，然后静脉注射牙龈假单胞菌381。这些动物在11或14周后被安乐死。对每只动物近端主动脉动脉粥样硬化病变进行组织形态学分析，并测定血清40-kDa omp特异性抗体和细胞因子浓度。与未感染的小鼠相比，感染牙龈假单胞菌的Apoe（shl）小鼠的主动脉窦被动脉粥样硬化斑块覆盖的区域以及血清中炎症细胞因子和趋化因子的水平都有所增加。相比之下，与未免疫的动物相比，40 kda的OMP加CT鼻腔免疫显著减少了主动脉窦动脉粥样硬化斑块的积聚，降低了血清细胞因子和趋化因子的水平。鼻腔免疫还可诱导40 kda的omp特异性血清免疫球蛋白G （IgG）和唾液IgA抗体应答。这些发现表明，全身感染牙龈卟啉单胞菌可加速Apoe（shl）小鼠的动脉粥样硬化，40 kda OMP加CT可能是一种有效的鼻腔疫苗，可减少高脂血症小鼠模型中牙龈卟啉单胞菌加速的动脉粥样硬化。
Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. We assessed the potential of a nasal vaccine against P. gingivalis infection for the prevention of atherosclerosis. Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice were nasally immunized with the 40-kDa outer membrane protein (OMP) of P. gingivalis plus cholera toxin (CT) as adjuvant and then challenged intravenously with P. gingivalis strain 381. The animals were euthanized 11 or 14 weeks later. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum concentrations of 40-kDa OMP-specific antibodies and cytokines were determined. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of inflammatory cytokines and chemokines were increased in Apoe(shl) mice challenged with P. gingivalis compared to nonchallenged mice. In comparison, nasal immunization with 40-kDa OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to nonimmunized animals. Nasal immunization also induced 40-kDa OMP-specific serum immunoglobulin G (IgG) and saliva IgA antibody responses. These findings suggest that systemic infection with P. gingivalis accelerates atherosclerosis in Apoe(shl) mice, and 40-kDa OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in the hyperlipidemic mouse model.