Spontaneous PMN apoptosis in type 2 diabetes and the impact of periodontitis

Abstract

The purpose of this study was to test the hypothesis that peripheral blood neutrophils (PMN) exhibit delayed spontaneous apoptosis in individuals with diabetes mellitus type 2 (T2DM) and that the delay is exacerbated further among people who coexpress chronic periodontitis (CP). Seventy-three individuals were enrolled, including those with T2DM ( = 16), CP ( = 15), T2DM + CP ( = 21), and healthy volunteers ( = 21). PMN apoptosis was determined by flow cytometry using TUNEL and Annexin V assays. The activity of caspase-3, -8, and -9 was measured by colorimetric assay. PMN surface death receptor quantification was performed by flow cytometry staining with fluorescence-conjugated anti-CD120a (TNFR1) and anti-CD95 [Fas receptor (FasR)] antibody. Analysis of inflammatory markers in serum samples was performed using multiplexed sandwich immunoassays. In healthy volunteers and individuals with T2DM, CP, and T2DM + CP, spontaneous PMN apoptosis observed at 12 h reached 85.3 ± 3.1, 67.3 ± 3.9, 62.9 ± 3.5 and 62.5 ± 5.4%, respectively ( < 0.05). Caspase-3 activity was significantly reduced in individuals with T2DM and T2DM + CP ( < 0.05) when compared with healthy volunteers. Caspase-8 activity was also significantly decreased in CP and T2DM + CP ( < 0.05), associated with reduced cell-surface FasR, TNFRs, and Fas ligand (FasL) serum levels. Glucose alone was not observed to impact PMN apoptosis; simultaneous incubation with the receptor for advanced glycation endproducts (RAGE) agonist S100B induced significant PMN apoptosis ( < 0.05). These data support the premise that the inhibition of PMN apoptosis in individuals with T2DM occurs through an advanced glycation endproducts/RAGE ligand/receptor-mediated interaction.

Evaluation of Peripheral Blood Neutrophil Functions after an Oral Carbohydrate Overload in Obese and Insulin Resistant Horses

“…Interestingly, delayed neutrophil apoptotic rates have been reported in the studies mentioned above. Diverse studies in humans and mice had demonstrated that both, a dysfunctional metabolic status like type 2 diabetes mellitus and hyperglycemia are able to decrease the rate of neutrophil apoptosis [33,68,69]. Our study do not support similar ndings in the equine species, but it must be acknowledged that only spontaneous neutrophil apoptosis was assessed, in absence of stimuli reagents.…”

The role of caspase‐8, caspase‐9, and apoptosis inducing factor in periodontal disease

“…Manosudprasit et al . evaluated caspase‐3, ‐8, and ‐9 levels of peripheral blood neutrophils in patients with chronic periodontitis and type 2 Diabetes mellitus (T2DM).…”

“…Manosudprasit et al 31 evaluated caspase-3, -8, and -9 levels of peripheral blood neutrophils in patients with chronic periodontitis and type 2 Diabetes mellitus (T2DM). They reported that caspase-3 was significantly higher in T2DM patients with and without CP compared to healthy controls (P < 0.05).…”

The Neutrophil: Constant Defender and First Responder

“…Supporting the link between oral inflammation and systemic PMN responses, we found increased priming of PMNs in the circulation 1 week after cessation of oral hygiene practices, using a human model of experimental gingivitis ( 41 ). Another study showed that the presence of PD in diabetic patients exacerbated the suppression of apoptosis of circulating PMNs compared to diabetes alone ( 195 ). Although PMNs generally are recruited across the inflamed endothelium in a highly targeted manner to respond to an acute or chronic threat, what happens when a patient has an additional underlying inflammatory complication or comorbidity?…”