Altered Neutrophil Function in Localized Juvenile Periodontitis: Intrinsic or Induced?

Abstract

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‐α and/or IL1 β 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. J Periodontol 1996;67:337–344.

Polymorphisms Within the IL‐1 Gene Cluster: Effects on Cytokine Profiles in Peripheral Blood and Whole Blood Cell Cultures of Patients With Aggressive Periodontitis, Juvenile Idiopathic Arthritis, and Rheumatoid Arthritis

“…The association between IL‐1 genotypes and blood cell cytokine phenotypes in LAgP patients supports the hypothesis of a genetic background, at least for groups of patients with aggressive periodontitis 48,49 . Altered neutrophil function in LAgP has been discussed extensively since the 1970s 50 . Sera from LAgP patients altered the function of normal neutrophils: an effect that may be neutralized by anti‐TNF and anti–IL‐1 antibodies 51,52 .…”

Analysis of Human Gingival Tissue and Gingival Crevicular Fluid β‐Glucuronidase Activity in Specific Periodontal Diseases

“…9,10,14,15,[39][40][41] As indicated in some previous studies conducted on various GCF components, including enzymes, 15,[22][23][24][25]28 the highest GCF βG activity (with both expressions) was found in patients with EOP. This increase in EOP forms can be attributed to the hyperactive state and pronounced response of PMN as a consequence of severity of microbial virulence factors 1,42,43 and also to the lytic effect of more pathogenic subgingival bacteria on host cells leading to an intense host enzyme release. [44][45][46] Lysosomal release from host cells in response to plaque in the absence of phagocytosis 47 and the relatively increased production of oxygen metabolites acting as inactivators of inhibitors and activator of enzymes 43,48 and PMN priming in the gingival crevice 1 can also contribute to the enzymatic profile of GCF.…”

Extracellular 37-kDa Antigenic Protein from Actinobacillus actinomycetemcomitans Induces TNF-α, IL-1β, and IL-6 in Murine Macrophages

“…We measured the total quantity of each cytokine released from the macrophages over a 24-hour period. Cytokines are produced quickly in monocytes and macrophages stimulated with fimbriae protein (Hanazawa et al, 1991) or LPS (Agarwal et al, 1995), so our cytokine values might be influenced by the various cytokines which were released from macrophages in an autocrine and/or paracrine fashion. The amount of cytokines induced by the 37-kDa protein (from 0.5 to 50 pg/mL) was increased in a dose-dependent manner, and there were few changes in cell morphology over a 24-hour period of stimulation, so the 37-kDa protein samples did not induce cytotoxic effects on mouse macrophage.…”

“…No other uses without permission. jdr.sagepub.com Downloaded from stimulatory effects on macrophages (Barker and Holt, 1983), and induce the pro-duction of cytokines from immunocytes (Agarwal et al, 1995).…”