Medical Service, Ralph H Johnson VA Medical Center, Charleston, South Carolina, USA.
Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Lupus Sci Med. 2020 Oct;7(1). doi: 10.1136/lupus-2020-000418.
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.
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.
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.
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.
SLE 与内皮细胞功能障碍（ECD）有关。了解 ECD 如何导致中性粒细胞浸润肾小球对于寻找 SLE 的治疗靶点至关重要。本研究旨在确定来自活动期疾病患者的 SLE 血清诱导中性粒细胞黏附至肾小球内皮细胞和向其趋化的作用，以及与中性粒细胞趋化相关的由血清诱导的因子。
在疾病活动度较低和较高的配对纵向就诊期间采集 SLE 患者的血清。检查了 13 名 SLE 患者（5 名 SLE、5 名伴有高血压的 SLE (HTN) 和 3 名伴有 HTN 的狼疮肾炎 (LN)）和 10 名健康对照者（5 名伴有和 5 名不伴有 HTN）。测定了中性粒细胞对经血清处理的人肾小球内皮细胞（HRGEC）的黏附以及中性粒细胞向经血清处理的 HRGEC 条件培养基中的趋化作用，并定量了该条件培养基中细胞因子的水平。对与中性粒细胞迁移相关的由 SLE 和 LN 血清诱导的细胞因子进行了通路分析。
与对照血清相比，用 SLE 血清处理的 HRGEC 诱导的中性粒细胞趋化和黏附显著增加。在检查特定队列时，SLE HTN 和 LN HTN 比对照血清促进更大的中性粒细胞趋化，而 SLE HTN 和 LN HTN 比 SLE 血清促进更大的趋化。活动期就诊时的血清促进中性粒细胞趋化和黏附超过配对的非活动期就诊。SLE 血清处理的 HRGEC 分泌的血小板衍生生长因子-BB、白细胞介素 (IL)-15 和 IL-8 的水平与中性粒细胞趋化呈正相关。通路分析表明，LN 血清诱导的与内质网和氧化应激相关的途径重要。
SLE 血清诱导 HRGEC 表达促中性粒细胞趋化和黏附的介质，这些介质在疾病活动期增加，并与内质网和氧化应激途径的共同因子相关。这些发现突出了血清因子诱导的 ECD 在 SLE 和 LN 中的潜在重要性。
