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.
Montemurro
P
P
Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Patologia Generale, University of Bari, Bari, Italy.
Barbuti
G
G
Dundon
W G
WG
Del Giudice
G
G
Rappuoli
R
R
Colucci
M
M
De Rinaldis
P
P
Montecucco
C
C
Semeraro
N
N
Papini
E
E
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