Systemic disease and periodontitis: manifestations of neutrophil dysfunction

Deas, David E.; Mackey, Scott A.; McDonnell, Howard T.

doi:10.1046/j.0906-6713.2003.03207.x

Cited by 122 publications

(146 citation statements)

References 158 publications

(197 reference statements)

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“…9,10 Plg-deficient mice are more susceptible to systemic infection and bacterially induced arthritis than wild-type mice, and supplementation with Plg improves the bacterial killing ability. 26 Therefore, we estimated the number of bacteria in extracts prepared from homogenized mandibles from wild-type and Plg-deficient mice by plating on blood agar plates (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Plasmin Is Essential in Preventing Periodontitis in Mice

Sulniute

Lindh

Wilczyńska

et al. 2011

The American Journal of Pathology

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Periodontitis involves bacterial infection, inflammation of the periodontium, degradation of gum tissue, and alveolar bone resorption, which eventually leads to loss of teeth. To study the role of the broad-spectrum protease plasmin in periodontitis, we examined the oral health of plasminogen (Plg)-deficient mice. In wild-type mice, the periodontium was unaffected at all time points studied; in Plg-deficient mice, periodontitis progressed rapidly, within 20 weeks. Morphological study results of Plg-deficient mice revealed detachment of gingival tissue, resorption of the cementum layer, formation of necrotic tissue, and severe alveolar bone degradation. IHC staining showed massive infiltration of neutrophils in the periodontal tissues. Interestingly, doubly deficient mice, lacking both tissue-and urokinase-type plasminogen activators, developed periodontal disease similar to that in Plg-deficient mice; however, mice lacking only tissueor urokinase-type plasminogen activator remained healthy. Supplementation by injection of Plg-deficient mice with human plasminogen for 10 days led to necrotic tissue absorption, inflammation subsidence, and full regeneration of gum tissues. Notably, there was also partial regrowth of degraded alveolar bone. Taken together, our results show that plasminogen is essential for the maintenance of a healthy periodontium and plays an important role in combating the spontaneous development of chronic periodontitis. Moreover, reversal to healthy status after supplementation of Plg-deficient mice with plasminogen suggests the possibility of using plasminogen for therapy of periodontal diseases.

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Section: Discussionmentioning

confidence: 99%

Plasmin Is Essential in Preventing Periodontitis in Mice

Sulniute

Lindh

Wilczyńska

et al. 2011

The American Journal of Pathology

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“…As a negative control, cells were incubated with fluorescein-labeled nucleotides without terminal transferase. For assessment of advanced fragmentation of DNA (a marker of advanced apoptosis), genomic DNA was isolated by standard phenol:chloroform extraction and samples corresponding to 10 6 PMNs were analyzed in 1.5% agarose gel electrophoresis as described previously. 45 Purification and activation of gingipains.…”

Section: Methodsmentioning

confidence: 99%

“…Consequently, even very mild forms of PMN dysfunction can predispose affected individuals to severe forms of periodontitis. 10 However, it has also been well documented that tissue damage associated with periodontal disease is related to extensive accumulation of PMNs and the release of their destructive hydrolytic enzymes. [11][12][13] In this context, it is interesting to note that large number of PMNs in gingival crevicular fluid are found at different stages of necrosis.…”

mentioning

confidence: 99%

A new insight into phagocytosis of apoptotic cells: proteolytic enzymes divert the recognition and clearance of polymorphonuclear leukocytes by macrophages

et al. 2006

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The recognition of phosphatidylserine (PS) on the surface of any apoptotic cell is considered to be a key event for its clearance. We challenge this concept by showing that pretreatment of neutrophils with either host or bacterial protease affects their uptake by human monocyte-derived macrophages without having an effect on cell-surface PS presentation. Specifically, whereas preincubation of apoptotic neutrophils with cathepsin G or thrombin significantly inhibited their uptake, gingipains R or clostripain enhanced phagocytosis by macrophages. Moreover, bacterial proteinases sensitized healthy neutrophils for uptake by macrophages, whereas endogenous proteinases were unable to elicit this effect. This stimulation was apparently owing to the combined effect of proteolytic cleavage of an antiphagocytic signal (CD31) and the generation of a novel 'eat-me' signal on the neutrophil surface. These results argue that neutrophil recognition and phagocytosis by macrophages is mediated by a protein ligand whose proteolytic modification could affect the local inflammatory process.

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“…Although the etiology of aggressive periodontitis is still unclear, these subjects may be characterized by some defects in host defense system due to rapid disease progression (Kulkarni, & Kinane 2014). In fact, late‐stage human immunodeficient virus‐infected subjects and/or severe neutropenia are associated with severe periodontitis (Deas, Mackey, & McDonnell, 2003; Hajishengallis & Hajishengallis, 2014; Lucht, Heimdahl, & Nord, 1991). Because host‐defensive functions are severely impaired in these subjects, it is quite possible that substantial amounts of periodontal bacteria actually invade inflamed periodontal tissue, and the legion of subjects with aggressive periodontitis may also harbor such bacteria.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic effects against periodontal bacteria in organ cultured tissue

Takeshita

Haraguchi

Miura

et al. 2016

Clinical & Exp Dental Res

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Mechanical reduction of infectious bacteria by using physical instruments is considered the principal therapeutic strategy for periodontal disease; addition of antibiotics is adjunctive. However, local antibiotic treatment, combined with conventional mechanical debridement, has recently been shown to be more effective in periodontitis subjects with type 2 diabetes. This suggests that some bacteria may invade the inflamed inner gingival epithelium, and mechanical debridement alone will be unable to reduce these bacteria completely. Therefore, we tried to establish infected organ culture models that mimic the inner gingival epithelium and aimed to see the effects of antibiotics in these established models. Mouse dorsal skin epithelia were isolated, and periodontal bacteria were injected into the epithelia. Infected epithelia were incubated with test antibiotics, and colony‐forming ability was evaluated. Results indicated that effective antibiotics differed according to injected bacteria and the bacterial combinations tested. Overall, in organ culture model, the combination of amoxicillin or cefdinir and metronidazole compensate for the effects of less effective bacterial combinations on each other. This in vitro study would suggest effective periodontal treatment regimens, especially for severe periodontitis.

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Systemic disease and periodontitis: manifestations of neutrophil dysfunction

Cited by 122 publications

References 158 publications

Plasmin Is Essential in Preventing Periodontitis in Mice

Plasmin Is Essential in Preventing Periodontitis in Mice

A new insight into phagocytosis of apoptotic cells: proteolytic enzymes divert the recognition and clearance of polymorphonuclear leukocytes by macrophages

Antibiotic effects against periodontal bacteria in organ cultured tissue

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