title: Functional implication of the hydrolysis of platelet endothelial cell adhesion molecule 1 (CD31) by gingipains of Porphyromonas gingivalis for the pathology of periodontal disease.
abstract: Periodontitis is a response of highly vascularized tissues to the adjacent microflora of dental plaque. Progressive disease has been related to consortia of anaerobic bacteria, with the gram-negative organism Porphyromonas gingivalis particularly implicated. The gingipains, comprising a group of cysteine proteinases and associated hemagglutinin domains, are major virulence determinants of this organism. As vascular expression of leukocyte adhesion molecules is a critical determinant of tissue response to microbial challenge, the objective of this study was to determine the capacity of gingipains to modulate the expression and function of these receptors. Given the potential multifunctional role of platelet endothelial cell adhesion molecule 1 (PECAM-1) in the vasculature, the effect of gingipains on PECAM-1 expression by endothelial cells was examined. Activated gingipains preferentially down-regulated PECAM-1 expression on endothelial cells compared with vascular cell adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1, but the reduction in PECAM-1 expression was completely inhibited in the presence of the cysteine proteinase inhibitor TLCK (Nalpha-p-tosyl-l-lysine chloromethyl ketone). Endothelial monolayers treated with activated gingipains demonstrated progressive intercellular gap formation that correlated with reduced intercellular junctional PECAM-1 expression as determined by Western blotting and immunofluorescence microscopy. This was accompanied by enhanced transfer of both albumin and neutrophils across the monolayer. The results suggest that degradation of PECAM-1 by gingipains contributes to increased vascular permeability and neutrophil flux at disease sites.
authors.affiliation: Institute of Dental Research, Westmead Millennium Institute and Centre for Oral Health, Westmead Hospital, P.O. Box 533, Wentworthville, Sydney, NSW 2145, Australia. plwyun@yahoo.com
authors.forename: Peter L W
authors.initials: PL
authors.lastname: Yun
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Decarlo
authors.forename: Cheryl C
authors.initials: CC
authors.lastname: Chapple
authors.forename: Neil
authors.initials: N
authors.lastname: Hunter
mesh_terms: D018829:Adhesins, Bacterial; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D020556:Neutrophil Infiltration; D010510:Periodontal Diseases / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D019040:E-Selectin; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D003546:Cysteine Endopeptidases
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