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.

Estimation of Pentraxin‐3 Levels in the Gingival Tissues of Chronic and Aggressive Periodontitis Participants: An In Vivo Study

“…Immune defects have also been implicated in the pathogenesis of AgP. Several investigators have shown that patients with AgP display functional defects of polymorphonuclear leukocytes (PMNs), monocytes, or both 32‐34 . These defects can impair either the chemotactic attraction of PMNs to the site of infection or their ability to phagocytose and kill microorganisms.…”

Role of bacterial proteinases in matrix destruction and modulation of host responses

“…Neutrophils play a critical role in defense against periodontal pathogens, and intrinsic dysfunction or deficit of these cells predispose to the most severe forms of periodontal disease such as localized juvenile and generalized prepubertal periodontitis. The most common defects in neutrophil function are deficiencies in chemotaxis, phagocytosis, adherence and degranulation, but despite a vast literature the genetic trait(s) associated with the risk of these severe forms of disease are not fully understood (61,131,177,198,230,310). In addition, the precise molecular nature of neutrophil malfunction is known only in few cases but there is a consensus that these effects are relatively mild.…”

Analysis of host responses and risk for disease progression

“…(5,183,262) Finally, neutrophils undergo lysis or programmed cell death (apoptosis) after the completion of their primary protective function. Abnormalities in any of these steps might result in a delayed or less ef®cient host response to bacterial challenge (6,54,160,252,288).…”