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Experimental pathological study on roles of LPS-binding receptor CD14 in LPS-induced periodontal tissue destruction

LPS结合受体CD14在LPS诱导的牙周组织破坏中作用的实验病理学研究

基本信息

批准号：
10671702
负责人：
MIYAUCHI Mutsumi
金额：
$ 0.45万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Lipopolysaccharide (LPS) elicits various periodontal tissue responses including release of proinflammatory cytokines from host cells, recruitment of leukocytes and stimulation of osteoclastic bone resorption. CD14 has been known to be an important LPS-binding receptor which mediates these responses. The purpose of this project was to examine the role of CD14 in periodontal tissue destruction caused by LPS-challenge.1. A polyclonal antibody (RCD14) was produced in rabbit using a mixture of peptides corresponding to amino acids 26-45, 262-278 and 309-327 of rat CD14.2. We examined immunohistochemical localization of CD14 in rat periodontal tissues with or without topical application of LPS from E.Coli using RCD14. In the normal periodontal tissues, CD14 was expressed by macrophages in the perivascular area in addition to granulocytes and monocytes in alveolar bone marrow. In the junctional epithelium (JE) and sub-JE area, CD14-positive neutrophils and macrophages were resident. Oral epithelia including JE, were weakly positive for CD14. Epithelial remnants of Malassez were also positive for CD14.3. Effects of intraperitoneal injection of RCD14 on tissue responses at 3 hours and 3 days after topical application of LPS from E.Coli were studied. Histomorphometric analyses showed that the injection of RCD14 caused reduction in recruitment of neutrophils and macrophages innto JE and sub-JE area and decrease in appearance of osteoclasts along the alveolar bone margin, which induced by LPS application. Moreover transient production of TNF-α and MIP-2 by infiltrating cells and constitutive host cells, which seemed in LPS applied rats periodontal tissue, was not observed in rat with intraperitoneal injection of RCD14.Theses findings indicated that CD14 was expressed in various infiltrating and resident cells in the periodontal tissues and CD14 may play an important roles in periodontal inflammation and alveolar bone resorption caused by LPS-challenge.

脂多糖（LPS）可引起牙周组织的多种反应，包括宿主细胞释放促炎细胞因子、白细胞募集和刺激骨细胞骨吸收。已知CD 14是介导这些应答的重要LPS结合受体。本研究的目的是探讨CD 14在LPS刺激引起的牙周组织破坏中的作用。使用对应于大鼠CD 14.2的氨基酸26-45、262-278和309-327的肽的混合物在兔中产生多克隆抗体（RCD 14）。我们研究了CD 14在大鼠牙周组织中的免疫组织化学定位与或不局部应用从大肠杆菌LPS使用RCD 14。在正常牙周组织中，除了肺泡骨髓中的粒细胞和单核细胞外，血管周围区域的巨噬细胞也表达CD 14。在交界上皮（JE）和亚JE区，CD 14阳性中性粒细胞和巨噬细胞的居民。口腔上皮包括JE，CD 14弱阳性。Malassez的上皮残留物也为CD14.3阳性。研究了在局部应用来自大肠杆菌的LPS后3小时和3天腹膜内注射RCD 14对组织反应的影响。组织形态计量学分析显示，注射RCD 14后，LPS诱导的JE区和JE下区中性粒细胞和巨噬细胞的聚集减少，牙槽骨边缘破骨细胞沿着出现减少。此外，LPS作用后大鼠牙周组织中的浸润细胞和组成性宿主细胞也可瞬时产生TNF-α和MIP-2，结果表明，CD 14在牙周组织中的多种浸润细胞和驻留细胞中均有表达，CD 14可能在LPS诱导的牙周炎和牙槽骨吸收中起重要作用。挑战.