1985 Kreshover lecture. Molecular Factors Influencing Neutrophil Defects in Periodontal Disease

Abstract

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.

Hematological values in juvienile periodontitis patients in Ibadan, Nigeria

“…The initiation and progression of periodontitis do not always occur in the same manner, because the host defensive mechanism varies among patients and race (Page et al 1985;Genco et al 1986, Genco, 1992; hence this study was designed to evaluate the numerical value of the defense cells in juvenile and non-juvenile periodontitis patients compare with the expected normal values in Nigeria.…”

Genetic Control of Susceptibility toPorphyromonas gingivalis-Induced Alveolar Bone Loss in Mice

“…Studies involving monozygotic and dizygotic twins have suggested that about half of the population variance in disease could be accounted for by genetic factors (8,24). Increased susceptibility to periodontal disease is found in conjunction with several inherited diseases (10,28). Very recently, an interleukin-1 polymorphism has been reported to be a predictor of future severity in adult periodontal disease (19).…”

Cleavage of CD14 on Human Gingival Fibroblasts Cocultured with Activated Neutrophils Is Mediated by Human Leukocyte Elastase Resulting in Down-Regulation of Lipopolysaccharide-Induced IL-8 Production

“…This mechanism could exist in physiological conditions as a new negative feedback mechanism of inflammation. Early-onset periodontitis is characterized by severe, rapidly progressive, early-onset alveolar bone loss and familial aggregation (50). PMNs from early-onset periodontitis patients have been reported to produce much higher HLE than controls (51).…”