Platelet activation by Protease I of Porphyromonas gingivalis W83.
Porphyromonas gingivalis produces a trypsin-like enzyme, Protease I, which is thought to be an important virulence determinant of the organism in adult periodontal disease. Protease I is transiently inhibited by physiological inhibitors of human thrombin. The aim of the present work was to establish whether Protease I was able to mimic thrombin by activation of the thrombin receptor on human platelets. Protease I caused true platelet activation at concentrations comparable to thrombin as measured by aggregometry, morphology and fluorescence flow cytometric analysis of CD63 expression. The effect was blocked by protease inhibitors but not by anti-thrombin receptor antibodies which, by contrast, blocked platelet activation by thrombin. We conclude that the activation of platelets by P. gingivalis Protease I involves proteolysis, but not scission of the thrombin cleavage site of the thrombin receptor.
MRC Dental Research Unit, London Hospital Medical College, Whitechapel, UK.
M A
MA
Curtis
M
M
Macey
J M
JM
Slaney
G L
GL
Howells
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000472:pathogenicity; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000276:immunology; D018179:Receptors, Thrombin; D012697:Serine Endopeptidases / Q000494:pharmacology*; D060149:Tetraspanin 30; D013917:Thrombin / Q000494:pharmacology; D014774:Virulence
D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D060149:Tetraspanin 30; C082568:Protease I, Porphyromonas gingivalis W83; D012697:Serine Endopeptidases; D013917:Thrombin