Monocyte Differentiation in Localized Juvenile Periodontitis Is Skewed toward the Dendritic Cell Phenotype

Abstract

Several lines of evidence indicate that the monocytes of subjects with localized juvenile periodontitis (LJP) are functionally distinct from cells of age-and race-matched nonperiodontitis (NP) subjects. Among the abnormalities are the propensity to secrete large amounts of prostaglandin E 2 and the induction of immunoglobulin G2 (IgG2) antibodies. The experiments described here were performed to further characterize the LJP monocytes and to determine if these cells mature differently than NP monocytes. When adherent monocytes from LJP subjects were cultured in the presence of human serum, both macrophages and cells with the morphology of immature monocyte-derived dendritic cells (MDDC) were observed. Within 4 days the prevalence of the immature MDDC was approximately twofold higher in LJP cultures than in NP cultures. In addition to their dendritic morphology, these cells were CD11c ؉ and CD14 ؊ or CD14 low and stimulated potent autologous mixed leukocyte reactions, consistent with differentiation to the MDDC phenotype. Like LJP monocytes, cultures of MDDC generated with interleukin-4 and granulocyte-macrophage colony-stimulating factor selectively induced IgG2 in cultures of pokeweed mitogen-stimulated NP leukocytes. Together, these data suggest that the monocytes of LJP subjects have a propensity to differentiate into MDDC and that this differentiation may be related to the high levels of IgG2 that are observed in the sera of LJP subjects. As high levels of circulating IgG2 are correlated with less severe disease, the propensity of LJP monocytes to differentiate into MDDC may have important implications for both the host response against oral pathogens and the progression of LJP.Localized juvenile periodontitis (LJP) is a form of earlyonset periodontitis that tends to run in families. Several oral pathogens have been linked to the etiology of the disease, including Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis (4,22,36,37). However, mounting evidence suggests that alterations in the host response may contribute to the pathogenesis of LJP. Several studies have highlighted abnormalities in the myeloid compartment of LJP subjects. For example, LJP neutrophils exhibit reduced chemotactic and calcium responses (7, 10) and have altered diacylglycerol metabolism (32) compared to cells from nonperiodontitis (NP) individuals. The peripheral blood of LJP subjects contains abnormally large numbers of immature granulocytes, which express low levels of CD16 (25). It also appears that the monocytes of LJP subjects are somewhat abnormal, as these cells produce abnormally large amounts of prostaglandin E 2 (PGE 2 ) in response to stimulation with lipopolysaccharide (26, 30). Our group has been particularly intrigued by the unique relationship that appears to exist between LJP monocytes and antibody production.LJP patients exhibit elevated levels of circulating immunoglobulin G2 (IgG2) compared to age-and race-matched NP subjects (23). In contrast, the levels of other isotypes of IgG are similar in NP and L...

Differential Expression of Platelet-Activating Factor Acetylhydrolase in Macrophages and Monocyte-Derived Dendritic Cells

“…Most notably, the monocyte-derived lipid mediators, PAF and PGE 2 , were shown to induce IgG2 production, but had no effect on the production of IgG1 in a pokeweed mitogen-driven in vitro culture system. Furthermore, highly enriched MDDC cultures were shown to have a similar selective effect on IgG2 production (9). Together, these studies suggest that the outgrowth of MDDC in cultures of LJP monocytes may have important implications for the regulation of Ig subclass responses and that this regulation may be mediated through the levels of lipid mediators in the cultures.…”

“…Our interest in PAF metabolism in MDDC comes from studies of the immune response in localized juvenile periodontitis (LJP), a periodontal disease characterized by its circumpubertal onset and characteristic localized loss of supporting tissues around first molars and incisors (8). In a previous study we demonstrated that monocytes from LJP subjects have an increased propensity to differentiate into MDDC, while monocytes from healthy non-periodontitis (NP) subjects primarily differentiate into M (9). Moreover, LJP subjects have elevated levels of IgG2 Ab in their sera, and LJP monocytes secrete cytokines that selectively promote the production of this subclass of Ab (10,11).…”

Delineation of the Role of Platelet-Activating Factor in the Immunoglobulin G2 Antibody Response

“…IgG2 levels in supernatant fluids were determined by a sandwich ELISA as described previously (4). Briefly, Fc-specific goat anti-mouse antibody (10 l/ml) (ICN, Aurora, Ohio) in pH 9.6 carbonate buffer was used to coat the microtiter plates (Dynex, Chantilly, Va.).…”

“…2A and B). These observations are of particular interest because monocyte differentiation appears to be skewed to the DC phenotype in LAgP subjects (4). Indeed, PAFAH levels are lower in the adherent monocytes of LAgP subjects than in monocytes from race-matched NP controls (1).…”

Dendritic Cells, Antibodies Reactive with oxLDL, and Inflammation

“…In blood, or in sites infiltrated with blood, NK cells are the source of this rapid IFN-γ (24-hour) that promotes DC-IL-12. NK cells need IL-12 for Barbour et al (2002) optimal IFN-γ, and it appears that P. gingivalis-DC-NK interactions result in reciprocal activation and increased DC-IL-12 and NK cell-IFN-γ (Kikuchi et al, 2004(Kikuchi et al, , 2005(Kikuchi et al, , 2010. Both DCs and NK cells are necessary to get the rapid 24-hour IFN-γ needed to induce the P. gingivalis-specific IgG2 in recall responses in PBL cultures (Kikuchi et al, 2005).…”