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Proteolysis of ICAM-1 on Human Oral Epithelial Cells by Gingipains

¹ Department of Microbiology and Immunology and
² Department of Periodontics and Endodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan;
³ Division of Molecular Pathology, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Science, Kumamoto, Japan;
⁴ Department of Microbiology and Immunology, Institute of Molecular Biology, Jagiellonian University, Cracow, Poland; and
⁵ Department of Biochemistry, University of Georgia, Athens, GA, USA;

Correspondence: *corresponding author, sugawars{at}mail.cc.tohoku.ac.jp

Cysteine proteinases (gingipains) from Porphyromonas gingivalis are considered key virulence factors of severe periodontitis and host immune evasion. Since expression of intercellular adhesion molecule-1 (ICAM-1) on gingival epithelium is indispensable in polymorphonuclear leukocyte (PMN) migration at the site of periodontitis, we examined the effects of gingipains on the expression of ICAM-1 on human oral epithelial cell lines (KB and HSC-2) by flow cytometry and Western blotting. We found that three purified forms of gingipains efficiently reduced ICAM-1 expression on the cells in a time- and dose-dependent manner. Gingipains reduced the expression on fixed cells and degraded the ICAM-1 in the cell membranes, indicating that the reduction resulted from direct proteolysis. They then disturbed the ICAM-1-dependent adhesion of PMNs to the cells. These results indicate that gingipains cleave ICAM-1 on oral epithelial cells, consequently disrupting PMN-oral epithelial cell interaction, and are involved in immune evasion by the bacterium in periodontal tissues.

Key Words: gingipains • proteolysis • ICAM-1 • oral epithelial cells • neutrophil adhesion

Journal of Dental Research, Vol. 82, No. 10, 796-801 (2003)
DOI: 10.1177/154405910308201007


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