Antigen Presenting Cells Up-regulate PGRP3&4 Expression in Inflamed Gingival Tissue

Objectives: Patterns recognition receptors (PRRs) play crucial roles in periodontal inflammation. Peptidoglycan recognition proteins 3 & 4 (PGRP3&4) are novel secreted PRRs that have antimicrobial activity under specific conditions. Additionally PGRP3&4 promotes anti-inflammatory activity. We have previously shown that PGRP3&4 levels are elevated in saliva of patients with chronic periodontitis. PGRP3&4 are thought to be predominantly expressed by epithelial cells. However this has not been confirmed in gingival tissue. Objective: To study and to identify the cells that express PGRP3&4 and the distribution pattern of these cells in inflamed and healthy gingival tissues, that were obtained from around teeth and dental implants.
Methods: Methods: Gingival tissue biopsies were collected from routine surgical procedures on patients with periodontitis (n=10), peri-implantitis (n=2) and healthy individuals (n=22). Expression of PGRP3&4 was assessed using immunohistochemistry and double immunofluorescence techniques. Appropriate negative and positive controls were used.
Results: Results: PGRP3&4 are upregulated primarily in inflamed gingival tissues, but not in histologically healthy gingival tissue. Surprisingly, PGRP3&4 expression were limited to connective tissue with no expression observed in epithelium. PGRP3&4 positive cells appears to be distributed throughout the connective tissue. Distinctively positive cells are observed in the rete ridges/papillary projections. PGRP3 prevalence and intensity were higher compared to PGRP4 consistent with levels of inflammation and similar to levels in saliva. Histo-morphologically, the positive cells appears to be antigen presenting cells and/or lymphocytes. Serial sections demonstrate that many of PGRP3&PGRP4 positive cells also express s100. Double immunofluroscence reveals that PGRP3 and PGRP4 are co-expressed in only few of the cells, while PGRP3 positive cells are found in greater numbers compared to PGRP4, consistent with immunohistochemistry. Peri-implant inflamed tissue have greater number of cells with PGRP3&4 expression.
Conclusions: Conclusions: PGRP3&4 expression is elevated with inflammation in periodontal and peri-implant connective tissues. PGRP3&4 may play significant role in antigen presentations during periodontal inflammation.