Neutrophil-derived reactive oxygen species in SSc

Reactive oxygen species (ROS) are implicated in the pathogenesis of SSc. Neutrophils constitute a major source of ROS during inflammation. Here, we examined endogenous and stimulated ex vivo ROS production of SSc neutrophils compared with control neutrophils with and without prior priming with TNF-α...

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Bibliographic Details
Published in:Rheumatology (Oxford, England) England), 2012-07, Vol.51 (7), p.1166-1169
Main Authors: BARNES, Theresa C, ANDERSON, Marina E, EDWARDS, Steven W, MOOTS, Robert J
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Diseases of the osteoarticular system
Endothelium, Vascular - immunology
Endothelium, Vascular - metabolism
Endothelium, Vascular - physiopathology
Female
Follow-Up Studies
Humans
Luminescence
Male
Medical sciences
Middle Aged
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Oxidative Stress
Reactive Oxygen Species - metabolism
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Scleroderma, Systemic - blood
Scleroderma, Systemic - immunology
Scleroderma, Systemic - physiopathology
Vasodilation
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Summary:Reactive oxygen species (ROS) are implicated in the pathogenesis of SSc. Neutrophils constitute a major source of ROS during inflammation. Here, we examined endogenous and stimulated ex vivo ROS production of SSc neutrophils compared with control neutrophils with and without prior priming with TNF-α. ROS generation was measured using luminol-enhanced chemiluminescence. Neutrophils isolated from SSc patients and healthy controls were unprimed or were primed with TNF-α. ROS production was stimulated in vitro with phorbol 12-myristate 13-acetate (PMA) and formyl-met-leu-phe (fMLP). To examine the effects of serum mediators on ROS generation, control neutrophils were also stimulated with SSc or control serum. Neutrophil stimulation with PMA and fMLP resulted in a greater increase in ROS generation in SSc neutrophils compared with controls. However, unstimulated SSc neutrophils generated lower levels of ROS than controls. SSc neutrophils demonstrated an increased response to fMLP in the absence of in vitro TNF-α priming indicating priming of SSc neutrophils in vivo. SSc serum did not stimulate neutrophil ROS generation in vitro. SSc neutrophils are primed for ROS generation. Neutrophils binding to activated endothelium in SSc, may induce local production of ROS, perpetuating endothelial dysfunction and mediating fibrosis.
ISSN:1462-0324
1462-0332
DOI:10.1093/rheumatology/ker520