Simultaneous assessment of complement components C3, C4, and B and their cleavage products in human gingival fluid

Abstract

The activation of the complement system is an important host-mediated mechanism in the initiation and progression of inflammation. Complement cleavage products have been reported in gingival fluid obtained from periodontitis lesions suggesting a potential role for the activation of the alternative and/or classical complement pathways in the pathogenesis of periodontitis. Using the multi-layer crossed immunoelectrophoresis technique, the eflect of periodontal therapy on complement conversion of C3, C4, and B was assessed in 37 sites in 9 patients. Patients selected for study had moderate-severe periodontitis as confirmed by clinical measurements of plaque, gingival inflammation, bleeding on probing, suppuration, pocket depth, and loss of attachment. Gingival fluid and clinical indices were obtained from representative sites prior to treatment and again 2-4 weeks following extensive periodontal scaling and root planing.Periodontal therapy resulted in a statistically significant decrease in all clinical parameters of inflammation. The percentage of C3 conversion decreased significantly from 70.0% to 37.5% with therapy (p = 0.0001) while the reference protein, transferrin, did not significantly change. C4 conversion to C4c was never observed and total C4 was not significantly altered by therapy. Changes in B conversion to Bb could not be evaluated because the Bb precipitate was too small to measure reproducibly. These results suggested that complement activation, as measured by C3 conversion to C3c, decreased in gingival fluid following periodontal therapy and suggested a role for complement activation in the pathogenesis of inflammatory periodontal disease.anisms including chemotactic attraction of Address:

Gingival crevicular fluid proteomes in health, gingivitis and chronic periodontitis

“…With their extensive role in the immune response , it is no surprise that they have been identified in gingival crevicular fluid proteome studies in healthy , experimental gingivitis and periodontitis sites . After periodontal treatment, a decrease in C3 levels has been observed, consistent with health . Activation of complement has been verified by raised levels of cleaved complement and its precursors in gingivitis and periodontitis .…”

Extracellular neutrophil traps in periodontitis

“…However, neither the dispersal of subgingival plaque bacteria, nor the fate of dispersed crevicular bacteria has been investigated until now. The existence of myriads of solitary bacteria in the crevice is difficult to explain by the multiplication of planktonic bacteria there, as a few planktonic bacteria could be (i) flushed out by the crevicular exudate outflow (3), (ii) phagocytosed, or (iii) harmed by complement activation (34) and other blood serum bactericides. By contrast, dispersal from the subgingival plaque can result in the production of a huge number of solitary bacteria in the crevice for a certain period of time.…”

Complement and periodontitis

“…On the other hand, the central complement component C3 is among the top 5% genes that are most strongly downregulated following periodontal therapy [68]. Moreover, C3 conversion to C3c in GCF decreases dramatically after periodontal therapy [69]. Mechanistically, local complement activation may promote periodontal inflammation predominantly via C5a-induced vasodilation, increased vascular permeability and flow of inflammatory exudate, and chemotactic recruitment of inflammatory cells, especially neutrophils [70, 71] (Fig.…”