A potential role of an intracellular signaling defect in neutrophil functional abnormalities and promotion of tissue damage in patients with localized juvenile periodontitis.

Abstract

Localized juvenile periodontitis is a destructive form of periodontal inflammatory disease which has its onset at puberty. The etiopathology of the disease is still unclear but neutrophils have been suggested to play a major role both in the production and development of the disorder. About 70% of the patients with localized juvenile periodontitis exhibit neutrophil functional abnormalities, such as decreased chemotaxis and phagocytosis. Interestingly, it has been frequently reported that the same hypoactive cells show an enhanced respiratory burst response and increased adhesion. Several possible mechanisms explaining neutrophil anomalies in localized juvenile periodontitis have been proposed. These include the presence of soluble serum factors capable of modulating neutrophil function, altered cell-surface receptor expression and/or function, and a change in the post-receptor signaling events. Recently, a growing evidence has accumulated showing that the diacylglycerol metabolism could be altered in neutrophils from patients with localized juvenile periodontitis. This change, which may be due to a defect in a major diacylglycerol metabolizing enzyme, diacylglycerol kinase, results in enhanced accumulation of diacylglycerol in activated cells. Because diacylglycerol is an endogenous activator of protein kinase C, the increased and prolonged generation of diacylglycerol could lead to abnormal pattern of protein kinase C-regulated neutrophil functions, explaining the parallel hypo- and hyperactivities.