Macrophage Depletion Abates Porphyromonas gingivalis-Induced Alveolar Bone Resorption in Mice
Macrophage Depletion Abates Porphyromonas gingivalis-Induced Alveolar Bone Resorption in Mice
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DOI：
10.4049/jimmunol.1400853
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发表时间：
2014-09-01
影响因子：
4.4
通讯作者：
Reynolds, Eric C.
中科院分区：
文献类型：
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作者：
Lam, Roselind S.;O'Brien-Simpson, Neil M.;Reynolds, Eric C.
巨噬细胞在牙周炎免疫病理中的作用尚不清楚。在这项研究中，我们发现口腔内接种牙龈卟啉单胞菌会导致小鼠感染，牙槽骨吸收，牙龈和颌下淋巴结组织中F4/80(+)巨噬细胞显著增加。在BALB/c和C57BL/6小鼠中，使用氯屈膦酸脂质体去除巨噬细胞可显著减少F4/80(+)巨噬细胞在牙龈和颌下淋巴结组织中的渗透，显著(p<；0.01)减少Pggvalis诱导的骨吸收。在两个品系的小鼠中，去巨噬细胞组的牙龈假单胞菌特异性抗体亚类和血清细胞因子[IL-4、IL-10、干扰素-γ和IL-12(P70)]反应显著降低(p<；0.01)。去除巨噬细胞可显著降低牙周炎的感染率，且牙周炎的感染率与牙槽骨吸收程度显著相关。Pggvalis感染后，牙周渗出液中主要的巨噬细胞表型为M1巨噬细胞(CD86(+))，而不是M2巨噬细胞(CD206(+))。牙龈假单胞菌可诱导小鼠巨噬细胞分泌IL-1β、IL-6、IL-10、IL-12(P70)、嗜酸性粒细胞趋化蛋白-1、G-CSF、GM-CSF、巨噬细胞趋化蛋白-1、巨噬细胞炎性蛋白-α、巨噬细胞炎性蛋白-α、肿瘤坏死因子-α等。综上所述，Pggivalis感染可诱导牙周组织中功能性/炎性M1巨噬细胞的渗入和牙槽骨吸收。巨噬细胞去除通过调节宿主免疫反应来减少牙龈假单胞菌感染和牙槽骨吸收。
The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80(+) macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80(+) macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis-induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis-specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-gamma, and IL-12 (p70)] responses were significantly (p < 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86(+)), rather than M2 macrophages (CD206(+)), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1 beta, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-alpha and -beta, and TNF-alpha in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.