Helicobacter pylori neutrophil-activating protein stimulates tissue factor and plasminogen activator inhibitor-2 production by human blood mononuclear cells.
Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor that activates phagocytic NADPH-oxidase. The effect of HP-NAP on the production of tissue factor (TF), plasminogen activator inhibitor-2 (PAI-2), and urokinase-type plasminogen activator (u-PA) by human blood mononuclear cells (MNC) was evaluated by using functional and immunological assays and mRNA analysis. HP-NAP induced time- and dose-dependent increases in TF and PAI-2, with a maximal effect at 300 nmol/L (>15-fold increase in antigens). No changes in u-PA were observed. When whole bacteria were used, an H. pylori mutant lacking HP-NAP was significantly less active than the wild-type strain. MNC from a patient with chronic granulomatous disease behaved as do normal cells, which indicates that HP-NAP effects can occur independently of NADPH-oxidase. HP-NAP, by inducing the coordinate expression of cell procoagulant and antifibrinolytic activities, might favor fibrin deposition and contribute to the inflammatory reaction of gastric mucosa elicited by H. pylori.
Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Patologia Generale, University of Bari, Bari, Italy.
P
P
Montemurro
G
G
Barbuti
W G
WG
Dundon
G
G
Del Giudice
R
R
Rappuoli
M
M
Colucci
P
P
De Rinaldis
C
C
Montecucco
N
N
Semeraro
E
E
Papini
D001426:Bacterial Proteins / Q000494:pharmacology*; D015152:Blotting, Northern; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000276:immunology; D016480:Helicobacter pylori / Q000737:chemistry*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D009154:Mutation; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*
D001426:Bacterial Proteins; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; C092412:neutrophil-activating protein A, Helicobacter pylori; D014568:Urokinase-Type Plasminogen Activator