Chae P, Im M, Gibson F, Jiang Y, Graves D T
Department of Endodontics, Boston University School of Dental Medicine, Massachusetts 02118, USA.
Infect Immun. 2002 Jun;70(6):3164-9. doi: 10.1128/IAI.70.6.3164-3169.2002.
Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that induces monocyte recruitment in a number of different pathologies, including infection. To investigate the role of MCP-1 in protecting a host from a chronic interstitial polymicrobial infection, dental pulps of MCP-1(-/-) mice and controls were inoculated with six different oral pathogens. In this model the recruitment of leukocytes and the impact of a genetic deletion on the susceptibility to infection can be accurately assessed by measuring the progression of soft tissue necrosis and osteolytic lesion formation. The absence of MCP-1 significantly impaired the recruitment of monocytes, which at later time points was threefold higher in the wild-type mice than in MCP-1(-/-) mice (P < 0.05). The consequence was significantly enhanced rates of soft tissue necrosis and bone resorption (P < 0.05). We also determined that the MCP-1(-/-) mice were able to recruit polymorphonuclear leukocytes (PMNs) to a similar or greater extent as controls and to produce equivalent levels of Porphyromonas gingivalis-specific total immunoglobulin G (IgG) and IgG1. These results point to the importance of MCP-1 expression and monocyte recruitment in antibacterial defense and demonstrate that antibacterial defense is not due to an indirect effect on PMN recruitment or modulation of the adaptive immune response.
单核细胞趋化蛋白1(MCP-1)是一种重要的趋化因子,在包括感染在内的多种不同病理状况下可诱导单核细胞募集。为了研究MCP-1在保护宿主免受慢性间质性混合微生物感染中的作用,将MCP-1基因敲除小鼠和对照小鼠的牙髓接种六种不同的口腔病原体。在此模型中,通过测量软组织坏死和溶骨性病变形成的进展情况,可以准确评估白细胞的募集以及基因缺失对感染易感性的影响。MCP-1的缺失显著损害了单核细胞的募集,在后期时间点,野生型小鼠中的单核细胞募集量比MCP-1基因敲除小鼠高三倍(P < 0.05)。结果是软组织坏死和骨吸收的发生率显著增加(P < 0.05)。我们还确定,MCP-1基因敲除小鼠能够募集与对照小鼠相似或更多的多形核白细胞(PMN),并产生等量的牙龈卟啉单胞菌特异性总免疫球蛋白G(IgG)和IgG1。这些结果表明MCP-1表达和单核细胞募集在抗菌防御中的重要性,并证明抗菌防御并非由于对PMN募集的间接影响或适应性免疫反应的调节。