NADPH oxidase priming and p47phox phosphorylation in neutrophils from synovial fluid of patients with rheumatoid arthritis and spondylarthropathy.
Superoxide anion (O2(o)-)production by neutrophil NADPH oxidase participates in arthritic joint lesion formation. Proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin 8 (IL-8) and granulocyte/macrophage-colony stimulating factor (GM-CSF) have a priming effect on neutrophil NADPH oxidase activity. NADPH oxidase activation is dependent on phosphorylation of p47phox, a cytosolic component of the enzyme. We studied O2(o)-production and p47phox phosphorylation in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) according to TNFalpha, IL-8 and GM-CSF levels. O2(o)-production by neutrophils isolated from SF of all the arthritis patients (RA and SpA) was higher than that of circulating resting neutrophils and when stimulated with fMLP or PMA. In addition, p47phox was partially phosphorylated in SF neutrophils compared to circulating neutrophils. High levels of TNFalpha and IL-8 (but not GM-CSF) are detected in patient's SF (compared to circulating blood levels). TNFalpha levels were significantly higher in RA than in SpA SF. These results suggest that increased NADPH oxidase activity could be involved in arthritic joint inflammation through increased p47phox phosphorylation. This could be the result of the presence of high levels of priming agents such as TNFalpha and IL-8 but not GM-CSF.
El Benna
Jamel
J
INSERM U479 and Rheumatology Department, C.H.U. Xavier Bichat, 16 Rue Henri Huchard, 75018 Paris, France. benna@bichat.inserm.fr
Hayem
Gilles
G
Dang
Pham My-Chan
PM
Fay
Michéle
M
Chollet-Martin
Sylvie
S
Elbim
Carole
C
Meyer
Olivier
O
Gougerot-Pocidalo
Marie-Anne
MA
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D025242:Spondylarthropathies / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism
D010750:Phosphoproteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1