title: Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase.
abstract: Evidence from recent epidemiological studies suggests a link between periodontal infections and increased risk of atherosclerosis and related cardiovascular and cerebrovascular events in human subjects. One of the major pathogens of periodontitis, Porphyromonas gingivalis, has the ability to aggregate human platelets in platelet-rich plasma (PRP). Mechanism of P. gingivalis-induced platelet aggregation in PRP was investigated. Proteinase inhibitors toward Arg-gingipain (Rgp) and Lys-gingipain (Kgp) did not suppress P. gingivalis-induced platelet aggregation in PRP, whereas the Rgp inhibitor markedly inhibited P. gingivalis-induced platelet aggregation using washed platelets. Mutant analysis revealed that P. gingivalis-induced platelet aggregation in PRP depended on Rgp-, Kgp- and haemagglutinin A (HagA)-encoding genes that intragenically coded for adhesins such as Hgp44. Hgp44 adhesin on the bacterial cell surface, which was processed by Rgp and Kgp proteinases, was essential for P. gingivalis-induced platelet aggregation in PRP. P. gingivalis cell-reactive IgG in plasma, and FcgammaRIIa receptor and to a lesser extent GPIbalpha receptor on platelets were found to be a prerequisite for P. gingivalis-induced platelet aggregation in PRP. These results reveal a novel mechanism of platelet aggregation by P. gingivalis.
authors.affiliation: Division of Microbiology and Oral Infection, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakai
authors.forename: Yixin
authors.initials: Y
authors.lastname: Shi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ideguchi
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005816:Genetic Complementation Test; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D039421:Integrin alpha2 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000494:pharmacology; D010510:Periodontal Diseases / Q000382:microbiology; D010949:Plasma / Q000378:metabolism*; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D015703:Antigens, CD; D001426:Bacterial Proteins; C080568:Fc gamma receptor IIA; D000080867:Gingipain Cysteine Endopeptidases; D007074:Immunoglobulin G; D039421:Integrin alpha2; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011480:Protease Inhibitors; D017452:Receptors, IgG; D014357:Trypsin; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases; C099092:mocarhagin