Elevated platelet and leukocyte response to oral bacteria in periodontitis.

BACKGROUND: Periodontitis is associated with an increased risk for cardiovascular diseases (CVD), but the underlying mechanisms are poorly understood. Recently, we showed that platelets from periodontitis patients are more activated than those from controls. OBJECTIVE: Given the regularly occurring bacteremic episodes in periodontitis patients, we hypothesized that platelets and/or leukocytes from periodontitis patients are more sensitive to stimulation by oral bacteria, in particular the known periodontal pathogens, than platelets from control subjects. METHODS: Three-color flow cytometry analysis was performed to quantify activation of platelets (P-selectin, PAC-1, CD63) and leukocytes (CD11b) in whole blood from patients with periodontitis (n = 19) and controls (n = 18), with and without stimulation by oral bacteria. Phagocytosis was assessed by using green-fluorescent protein (GFP)-expressing Aggregatibacter actinomycetemcomitans (Aa). RESULTS: Neutrophils and monocytes were activated by all species of oral bacteria tested, but no differences were observed between patients and controls. In response to several species of oral bacteria, platelets from periodontitis patients showed, compared with controls, increased exposure of P-selectin (P = 0.027) and increased formation of platelet-monocyte complexes (P = 0.040). Platelet-leukocyte complexes bound and/or phagocytosed more GFP-Aa than platelet-free leukocytes (for neutrophils and monocytes, in both patients and controls, P < 0.001). CONCLUSIONS: In periodontitis, increased platelet response to oral bacteria is paralleled by increased formation of platelet-leukocyte complexes with elevated capacity for bacterial clearance. We speculate that activated platelets and leukocytes might contribute to increased atherothrombotic activity.

Expression of FcgammaRs and mCD14 on polymorphonuclear neutrophils and monocytes may determine periodontal infection.

Variance in expression of receptors for immunoglobulin G (FcgammaRs), complement (CR3) and lipopolysaccharide (mCD14) on polymorphonuclear neutrophils (PMNs) and monocytes might affect susceptibility for infection with certain pathogens in periodontitis, a chronic infectious disease of tooth-supportive tissues. Levels of FcgammaRI, IIa, III, CR3 and mCD14 on PMNs and monocytes were measured in 19 periodontitis patients and 18 healthy controls. Subgingival infection with Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) was determined. Activation of PMNs and monocytes in response to stimulation with Aa and Pg was assessed by means of change in mCD14 expression. Periodontitis is associated with an enrichment of the FcgammaRIII(+) monocytes (P = 0.015) with concomitant low mCD14 (P = 0.001). Unadjusted data showed that the subjects culture-positive for Aa (Aa(+)) had significantly lower expression of monocytic FcgammaRI (P = 0.005) and FcgammaRIIa (P = 0.015) than Pg(+) subjects. The FcgammaRI was still lower on monocytes from Aa(+) subjects after adjusting for the background factors (P = 0.037). PMNs from Aa(+) subjects responded in a hyper-reactive manner, in particular when stimulated with Aa (P = 0.011). Lower FcgammaRs expression by monocytes is related to a higher susceptibility of a subject to become infected with Aa. The higher proportion of FcgammaRIII(+) monocytes may be involved in the chronicity of this condition. Hyper-reactive PMNs in Aa(+) subjects may contribute to accelerated breakdown of tooth-supportive tissues.

Hyper-reactive PMNs in FcgammaRIIa 131 H/H genotype periodontitis patients.

BACKGROUND: Receptors for the Fc part of IgG (FcgammaRIIa) on polymorphonuclear leukocytes (PMN) mediate phagocytosis and cell activation. Previous results show that one of the genetic variants of the FcgammaRIIa, the 131 H/H, is associated with more periodontal breakdown than the R/R. This may be due to hyper-reactivity of the H/H-PMNs upon interaction with bacteria. AIM: To study whether the FcgammaRIIa genotype modifies the PMN reactivity in periodontitis patients. MATERIAL AND METHODS: A cohort of 98 periodontitis patients was genotyped. From these, 10 H/H and 10 R/R consented to participate. PMNs were incubated with immune serum-opsonized Actinobacillus actinomycetemcomitans (A.a.). Phagocytosis, degranulation (CD63 and CD66b expression), respiratory burst and elastase release were assessed. RESULTS: Patients of the H/H genotype showed more bone loss than those with the H/R or R/R genotype (p=0.038). H/H-PMNs phagocytosed more opsonized A.a. than did R/R-PMNs (p=0.019). The H/H-PMNs also expressed more CD63 and CD66b than did the R/R-PMNs (p=0.004 and 0.002, respectively) and released more elastase (p=0.001). CONCLUSIONS: The genotyping results confirm previous reports that more periodontal destruction occurs in the H/H genotype than in the H/R or R/R genotype. The functional studies indicate a hyper-reactivity of the H/H-PMN in response to bacteria, which may be one of several pathways leading to more periodontal breakdown.