Increased release of free oxygen radicals from peripheral neutrophils in adult periodontitis after Feγ‐receptor stimulation

Abstract

The release of free oxygen radicals and degranulation was studied in neutrophils from 14 patients with adult periodontitis and 14 age- and sex-matched healthy controls. The neutrophils were activated by Fc gamma-receptor stimulation, using Staphylococcus aureus opsonized with gamma globulin. Release of oxygen radicals was measured as luminol-enhanced chemiluminescence. Degranulation was assessed as release of elastase, measured with a specific substrate and as release of lactoferrin measured with ELISA. The neutrophils from the patients showed a significantly higher chemiluminescence and a slightly higher release of elastase, whereas the release of lactoferrin was the same in both groups. In contrast, the ratio between the 2 degranulation products, elastase and lactoferrin, was significantly higher in the group with periodontitis. A flow cytometric analysis of the membrane expression of the adhesion molecules CD 11a, CD 11b, CD 15, CD 16, CD 35 and Mel 14 showed no differences in the median immunofluorescence between the 2 groups. This study showed a more than 2-fold higher release of free oxygen radicals from Fc-gamma-receptor stimulated neutrophils compared with healthy controls, which indicates a specific neutrophil-associated host response in adult periodontitis.

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

“…Although IFN-␥ has previously been shown to "prime" for neutrophil ROS generation in a stimulusdependant manner (46), we now demonstrate that type I IFN can perform a similar function. Taken together, these data indicate that increased peripheral blood type I IFN levels in periodontitis patients have the potential to serve as a priming factor and could contribute to the reported neutrophil hyperresponsivity with respect to Fc␥R-mediated ROS generation (7)(8)(9)(10).…”

“…By using microarrays not tailored for the disease we were able to elucidate transcriptional changes that were previously not part of current understanding. These studies have identified several functional groups of genes up-regulated in periodontitis patients' neutrophils compared with healthy controls, providing a better understanding of the molecular processes underpinning this highly prevalent disease in which peripheral neutrophils generate increased levels of ROS in the presence and absence of stimulation (7)(8)(9)(10).…”

“…The resultant collateral host tissue damage to the supporting periodontal tissues leads to progressive periodontitis and ultimately culminates in tooth loss (6). Several studies have demonstrated that PBN from chronic periodontitis patients are not only hyperreactive, in response to Fc␥R stimulation by periodontal pathogens, but also hyperactive, with respect to baseline unstimulated ROS production (7)(8)(9)(10). Although a host molecular defect in intracellular lipid signaling may explain peripheral neutrophil ROS hyperreactivity in the relatively rare form of the disease, localized aggressive periodontitis (11), this mechanism does not explain the patient predisposition observed in chronic periodontitis.…”

“…Although a host molecular defect in intracellular lipid signaling may explain peripheral neutrophil ROS hyperreactivity in the relatively rare form of the disease, localized aggressive periodontitis (11), this mechanism does not explain the patient predisposition observed in chronic periodontitis. The underlying mechanism(s) responsible for the hyperinflammatory neutrophil phenotype seen in chronic periodontitis (the commonest form of the disease) is currently unknown, although analyses indicate that it is not a result of altered adhesion molecule (7) or Phox gene (10) expression, polymorphisms in Fc␥R (8,12), or in vitro priming by cytokines or LPS (13,14). Furthermore, the association of periodontitis with increased relative risk for cardiovascular disease, fatal coronary events (15), and ischemic stroke (16), and the demonstrable medium-term reductions in vascular endothelial dysfunction following aggressive periodontal therapies (17), emphasize the potential impact of inflammatory periodontitis on peripheral macrovascular disease.…”

How periodontal disease may contribute to cardiovascular disease

“…It has also been reported that peripheral polymorphonuclear leukocytes from periodontitis patients show more than two-fold higher chemiluminescence following Fcg receptor stimulation than healthy control polymorphonuclear leukocyte (14). This polymorphonuclear leukocyte hyperreactivity may be due to these cells moving in the circulation through periodontal lesions or may be a constitutive feature of pa-tients with periodontal disease.…”