Article Text
Abstract
Objectives SLE is associated with endothelial cell dysfunction (ECD). Understanding how ECD leads to neutrophil infiltration into glomeruli is essential to finding therapeutic targets for SLE. The aim of this study is to determine the effect of SLE serum from patients with active disease to induce neutrophil adhesion to and chemotaxis towards glomerular endothelial cells and factors induced by serum that associate with neutrophil chemotaxis.
Methods Patients with SLE had serum collected during paired longitudinal visits with lower and higher activity. 13 patients with SLE (5 SLE, 5 SLE with hypertension (HTN) and 3 SLE lupus nephritis (LN) and HTN), and 10 healthy controls (5 with and 5 without HTN) were examined. The adhesion of neutrophils to serum-treated human renal glomerular endothelial cells (HRGECs) or chemotaxis of neutrophils towards conditioned media from serum-treated HRGECs was determined, and levels of cytokines in this conditioned medium were quantified. Pathway analysis of cytokines induced by SLE and LN serum that associated with neutrophil migration was performed.
Results HRGECs treated with SLE serum induced significantly greater neutrophil chemotaxis and adhesion compared with control serum. When examining specific cohorts, SLE HTN and LN HTN promoted greater neutrophil chemotaxis than control serum, while SLE HTN and LN HTN promoted greater chemotaxis than SLE serum. Serum from active disease visits promoted neutrophil chemotaxis and adhesion over paired inactive visits. Levels of platelet-derived growth factor-BB, interleukin (IL)-15 and IL-8 secreted by SLE serum-treated HRGECs positively correlated with neutrophil chemotaxis. Pathway analysis suggested that LN serum induced pathways important in endoplasmic reticulum and oxidative stress.
Conclusions SLE serum induces expression of mediators by HRGECs that promote neutrophil chemotaxis and adhesion, which increases during disease activity, and associates with factors common to pathways of endoplasmic reticulum and oxidative stress. These findings highlight the potential importance of serum factor-induced ECD in SLE and LN.
- lupus nephritis
- chemokines
- inflammation
- lupus erythematosus
- systemic
- cytokines
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Footnotes
Contributors JO conceived the idea and directed the project. DR and MM designed and performed the experiments, derived the models and analysed the data. DR and JO wrote the manuscript in consultation with MM.
Funding This work was supported by funding from the Department of Veterans Affairs (CXC001248-01A2 (Oates)). Data and materials as well as personnel time were made possible by the following funding: K08AR002193 (Oates)), NIH NIAMS P60AR062755 and NIAMS P30AR072582 (Oates).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the Medical University of South Carolina Institutional Review Board protocols: Pro00052903 Pro00056002. All human subject research was in compliance with the Helsinki Declaration. Subjects were enrolled after written informed consent was provided.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.
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