血小板在牙周炎宿主免疫炎症反应中的作用

Platelets as specialized inflammatory cells play important role in the host responses. Platelet and leukocyte interaction is a critical step in activation and recruitment of leukocyte to infected lesion in infectious disease. Previous work by our group showed that platelet activation response to periodontal pathogen and inflammatory cytokine was paralleled by increased formation of platelet–leukocyte aggregates with the recruitment of platelets and leukocytes to inflamed gingiva in patients with periodontitis. Platelets adhering to leucocytes were found in inflamed gingival biopsies. Therefore, we hypothesize that the interaction between platelets and leucocytes is a critical step in the activation and recruitment of leucocytes to infected periodontal tissues of periodontitis for immunopathological responses. In present study, experimental periodontitis of C57BL/6 wild-type mice is induced to investigate the localization and distribution of platelets in inflammatory periodontal tissues. To test the hypothesis that platelets affect leukocyte adhesion to vessels and promote the recruitment of leukocytes in inflamed periodontal tissues, we first induce transient depletion of platelets by antiplatelet serum, inhibit platelet activation using antiplatelet drugs, and in order to prevent platelet binding to leukocyte using blocking antibody, to explore the contribution of platelet in leukocyte infiltrate in the periodontium. Finally, we examine whether P-selectin mediated platelet and leucocyte interactions. To search for the role of platelets in host responses to periodontal infection may lead to novel approaches for the treatment of periodontitis.

血小板与白细胞的相互作用是白细胞活化和招募白细胞到炎症部位发挥免疫病理作用的关键步骤。我们前期研究率先发现牙周感染可引起血小板活化，血小板与白细胞黏附形成聚集体，而且在炎性牙龈组织中发现血小板聚集并与中性粒细胞黏附。由此推测血小板可能通过结合白细胞促进白细胞黏附、滚动、迁移到牙周组织，介导宿主的免疫炎症反应。本研究将利用实验性牙周炎小鼠模型，观察在牙周炎发生发展中血小板在牙周组织中浸润和分布的情况；通过减少血小板数目，探究血小板对白细胞黏附迁移的影响；并通过抑制血小板活化、阻断血小板-白细胞的相互作用，以明确活化血小板与白细胞的结合促进白细胞黏附迁移到牙周局部组织；然后在敲除血小板与白细胞结合受体的小鼠实验性牙周炎模型中，利用活体成像系统深入探讨血小板与白细胞在牙周炎中相互作用的分子机制。本研究结果将有助于深入了解血小板在牙周炎的宿主免疫炎症反应中的作用，为今后的临床精准干预治疗提供依据。

血小板与白细胞的相互作用是白细胞活化和招募白细胞到炎症部位发挥免疫病理作用的关键步骤。我们前期研究发现牙周感染可引起血小板活化，血小板与白细胞黏附形成聚集体，而且在炎性牙龈组织中发现血小板聚集并与中性粒细胞黏附。由此推测血小板可能通过结合白细胞促进白细胞黏附、滚动、迁移到牙周组织，介导宿主的免疫炎症反应。本研究利用实验性牙周炎小鼠模型，观察在牙周炎发生发展中血小板在牙周组织中浸润和分布的情况；通过抑制血小板活化、阻断血小板-白细胞的相互作用，明确活化血小板与白细胞的结合促进白细胞黏附迁移到牙周局部组织；并通过体内外研究探究龈沟液中的血小板与牙周致病菌和中性粒细胞的关系及可能的机制。本研究通过构建实验性牙周炎小鼠模型，模拟牙周炎的发生发展过程，观察到血小板参与牙周炎的发生发展，及其与白细胞的相互作用；进一步通过抑制血小板活化，明确血小板活化在牙周炎免疫炎症反应中的促进作用。体内外的研究也证实血小板具有一定的抗菌作用，既可以通过吞噬或聚集直接作用于牙周致病菌，也可以通过促进中性粒细胞胞外陷阱的形成间接作用于牙周致病菌。综上所述，本研究发现血小板在牙周炎免疫炎症反应及调控白细胞生物学中发挥重要作用；血小板和白细胞之间的相互作用是机体的检查点：血小板向白细胞传递了牙周组织存在感染的信息，促进白细胞迁移到牙周组织，抵抗感染同时也导致病理学变化。