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

Abstract

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.

Fig. 1

(a) Identification of PMNs and monocytes by whole blood flow cytometry. (b, c) Representative dot plots of monocytes in whole blood from (b) one periodontitis patient and (c) one control subject. The fraction of FcγRIII⁺ monocytes (above fluorescence threshold on the y-axis) from the total monocyte population was 32·9% in the periodontitis patient and 15·3% in the control subject.

Fig. 2

PMN and monocyte expression of (a) FcγRI, (b) FcγRIIa, (c) FcγRIII, (d) CR3, (e) mCD14 and (f) %s of FcγRIII⁺ monocytes for controls (open bars, n = 18) and periodontitis patients (closed bars, n = 19). Values are means ± standard deviation. ^aPatients have lower monocytic mCD14 than controls (P = 0·001). ^bPatients have higher % of FcγRIII⁺ monocytes (P = 0·015).

Fig. 3

mCD14 and % FcγRIII⁺ monocytes in (a) controls (open symbols) and (b) periodontitis patients (closed symbols). Each symbol represents one subject. There was an overall correlation between mCD14 and % FcγRIII⁺ monocytes (Pearson's correlation coefficient r = −0·473, P = 0·003), mainly because of a strong correlation in patients (r = −0·618, P = 0·005), while controls showed no correlation (r = −0·124, P = 0·624).

Fig. 4

PMN and monocyte expression of (a) FcγRI, (b) FcγRIIa, (c) FcγRIII, (d) CR3 and (e) mCD14 for Aa^-Pg^- subjects (open bars, n = 18), Aa⁺ subjects (bright grey bars, n = 9), Pg⁺ subjects (dark grey bars, n = 7), and Aa⁺Pg⁺ subjects (closed bars, n = 3). Values are means ± standard deviation; Aa (A. actinomycetemcomitans), Pg (P. gingivalis). ^aOn panel (a), monocytes: P = 0·005 for the overall anova; Aa⁺ subjects have lower monocytic FcγRI than Pg⁺ (post hoc P = 0·004). ^bOn panel (b), monocytes: P = 0·015 for the overall anova; Aa⁺ subjects have lower monocytic FcγRIIa than Pg⁺ (post hoc P = 0·009).

Fig. 5

Percentage change of mCD14 expression on PMNs and monocytes in response to (a) A. actinomycetemcomitans (Aa) or (b) P. gingivalis (Pg). Whole blood was incubated for 60 min with Aa or Pg. Data are means ± standard deviation for Aa^-Pg^- subjects (open bars, n = 18), Aa⁺ subjects (bright grey bars, n = 9), Pg⁺ subjects (dark grey bars, n = 7), and Aa⁺Pg⁺ subjects (closed bars, n = 3). ^a,bOn panel (a), PMN activation: P = 0·011 for the overall anova; Aa⁺ subjects have higher levels of mCD14 after Aa stimulation than Aa^-Pg^- subjects (post hoc P = 0·021) and Pg⁺ subjects (post hoc P = 0·022).