Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression

The thrombotic potential of oral pathogens

In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets

Reduced platelet hyper-reactivity and platelet-leukocyte aggregation after periodontal therapy

Background: Platelets from untreated periodontitis patients are hyper-reactive and form more platelet-leukocyte complexes compared to cells from individuals without periodontitis. It is not known whether the improvement of the periodontal condition achievable by therapy has beneficial effects on the platelet function. We aimed to assess the effects of periodontal therapy on platelet reactivity. Methods: Patients with periodontitis (n=25) but unaffected by any other medical condition or medication were included and donated blood before and after periodontal therapy. Reactivity to ADP or oral bacteria was assessed by flow cytometric analysis of membrane markers (binding of PAC-1, P-selectin, CD63) and platelet-leukocyte complex formation. Reactivity values were expressed as ratio between the stimulated and unstimulated sample. Plasma levels of soluble (s) P-selectin were determined by enzyme-linked immunosorbent assay (ELISA). Results: Binding of PAC-1, the expression of P-selectin and CD63 in response to the oral bacterium P. gingivalis were lower at recall (1.4±1.1, 1.5±1.2, and 1.0±0.1) than at baseline (2.7±4.1, P=0.026, 6.0±12.5, P=0.045, and 2.7±6.7, P=0.042, respectively). Formation of platelet-leukocyte complexes in response to P. gingivalis was also reduced at recall compared to baseline (1.2±0.7 vs. 11.4±50.5, P=0.045). sP-selectin levels were significantly increased post-therapy. Conclusions: In periodontitis patients, the improvement of the periodontal condition is paralleled by a reduction in platelet hyper-reactivity. We suggest that periodontal therapy, as an intervention for improved oral health, can facilitate the management of thrombotic risk, and on the long term can contribute to the prevention of cardiovascular events in patients at risk. Trial registration: Current Controlled Trials identifier ISRCTN36043780. Retrospectively registered 25 September 2013

Oral polymorphonuclear neutrophil contributes to oral health

Purpose of Review: Oral health is maintained in a dynamic equilibrium between the host immunity and the oral microbiome. Oral polymorphonuclear neutrophils (oPMNs) are important innate immune cells in the oral cavity. Recent Findings: The oPMNs play a co-controlling part in the maintenance of oral equilibrium. In human saliva, the oPMNs integrity is preserved, and their function remains unaffected. In general, oPMNs are in a higher state of baseline activation compared to peripheral PMNs. However, in periodontitis, the oPMNs' activation state can result in excessive release of damaging molecules in the extracellular environment. Summary: The presence of oPMNs may unwittingly negatively impact the integrity of the oral tissues. While most of the oPMN functions occur intracellularly, release of their potent active mediators into the extracellular environment may jeopardize oral homeostasis and its integrity. The dual nature of oPMNs, both beneficial and detrimental, remains a challenging and understudied topic