Genco R J, Van Dyke T E, Levine M J, Nelson R D, Wilson M E
J Dent Res. 1986 Dec;65(12):1379-91. doi: 10.1177/00220345860650120201.
Major advances in our understanding of the role of the neutrophil in host defense against periodontal organisms have been made through studies of localized juvenile periodontitis (LJP). Several lines of evidence suggest that LJP is an infectious process closely associated with Actinobacillus (Haemophilus) actinomycetemomitans as a causative agent, although other organisms may also participate. The immunologic profile of LJP patients suggests that a cell-associated neutrophil locomotory dysfunction is a key underlying immunodeficiency resulting in increased susceptibility to periodontal infection. In addition, LJP patients often exhibit cervical lymphadenopathy and IgG-hypergammaglobulinemia, and a markedly elevated antibody response to the infecting organism, A. actinomycetemcomitans, is found in the serum and crevicular fluid of most patients. Evaluation of the locomotory properties of LJP neutrophils shows that random migration and chemokinesis are normal; however, about 70% of the LJP patients suffer from a defect in chemotaxis, with their neutrophils responding poorly to bacterial chemotactic factors, synthetic chemotactic peptides, and complement fragments (C5a). Depressed chemotaxis of LJP neutrophils is paralleled by their reduced capacity to bind the synthetic chemotactic peptide N-formylmethionylleucylphenylalanine (FMLP), as well as C5a. Furthermore, there is a reduction in the amount of glycoprotein 110, a neutrophil membrane matrix component and differentiation antigen which is associated with FMLP- and possibly also C5a-mediated chemotaxis. Reduction of C5a and of FMLP ligand binding, decreased expression of GP-110, and reduced neutrophil chemotaxis are consistent with a stem cell maturation error in LJP patients. This is further supported by studies demonstrating increased expression of CR2, the C3d/EBV receptor, on peripheral blood neutrophils of LJP patients. CR2 receptors are normally present on immature human neutrophils but are lost during the maturation process. These alterations in neutrophil surface components and their reduced chemotaxis may result from a genetically determined abnormality. Studies demonstrating the familial nature of both the neutrophil chemotactic disorder and the clinical entity represented by localized juvenile periodontitis point to a strong role for genetic determinants in the disease which affect neutrophil surface receptors.
通过对局限性青少年牙周炎（LJP）的研究，我们在理解中性粒细胞在宿主抵御牙周病原体中的作用方面取得了重大进展。几条证据表明，LJP是一种与伴放线放线杆菌（嗜血性放线杆菌）作为病原体密切相关的感染性疾病，尽管其他微生物也可能参与其中。LJP患者的免疫特征表明，细胞相关的中性粒细胞运动功能障碍是导致对牙周感染易感性增加的关键潜在免疫缺陷。此外，LJP患者常表现出颈部淋巴结病和IgG型高球蛋白血症，并且在大多数患者的血清和龈沟液中发现对感染病原体伴放线放线杆菌的抗体反应明显升高。对LJP中性粒细胞运动特性的评估表明，随机迁移和化学增活作用正常；然而，约70%的LJP患者存在趋化性缺陷，其中性粒细胞对细菌趋化因子、合成趋化肽和补体片段（C5a）反应不佳。LJP中性粒细胞趋化性降低与其结合合成趋化肽N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）以及C5a的能力降低并行。此外，中性粒细胞膜基质成分和分化抗原糖蛋白110的量减少，该抗原与FMLP介导以及可能也与C5a介导的趋化性相关。C5a和FMLP配体结合减少、GP-110表达降低以及中性粒细胞趋化性降低与LJP患者的干细胞成熟错误一致。LJP患者外周血中性粒细胞上C3d/EBV受体CR2表达增加的研究进一步支持了这一点。CR2受体通常存在于未成熟的人类中性粒细胞上，但在成熟过程中会丢失。中性粒细胞表面成分的这些改变及其趋化性降低可能是由基因决定的异常引起的。证明中性粒细胞趋化性障碍和局限性青少年牙周炎所代表的临床实体具有家族性的研究表明，遗传决定因素在影响中性粒细胞表面受体的疾病中起重要作用。
