Altered neutrophil function in localized juvenile periodontitis: Intrinsic or induced?

LOCALIZED JUVENILE PERIODONTITIS (LJP) is an aggressive periodontal disease of familial nature. Neutrophils from a majority of patients with this disease exhibit decreased chemotaxis with increased adherence, oxidative burst, and degranulation in response to opsonized bacteria. It is proposed that the biological basis for these altered neutrophil functions in LJP may be due either to intrinsic cell abnormalities or to the effect of factors present in the sera of LJP patients, which can modulate neutrophil functions. LJP neutrophils exhibit a lower number of receptors for chemoattractants and GP-110 molecules which are known to facilitate chemotaxis. Furthermore, these cells exhibit lower signal transduction in response to a biological stimulus. These observations suggest that intrinsic cellular defects may be responsible for altered neutrophil functions in LJP. However, healthy neutrophils, when treated with very low concentrations of proinflammatory cytokines, also exhibit the characteristics of altered or ''defective'' LJP neutrophils. Additionally, healthy neutrophils, when treated with LJP serum, also exhibit many of the characteristics associated with LJP neutrophils. Attempts to identify these factors have shown that cytokines like TNF-alpha and/or IL-1 beta in LJP sera may be at least partially responsible for modulating neutrophil functions in LJP. These cytokines are primarily produced by activated macrophages, indicating a role for these cells in the etiology of LJP. The hyper-responsiveness of these cells to an immunologic challenge can result in local increases in cytokines leading to excessive bone loss and tissue damage at the site of infection, while systemic elevations in cytokines would lead to decreased neutrophil chemotaxis, both of which are observed in LJP. Present evidence indicates that neutrophil functions are indeed altered in the majority of LJP patients. However, the biological basis for the alteration may not be due to the neutrophils themselves but, rather, a consequence of an inherent hyperactive immune response during the host-pathogen interaction.