Ballantine Lucy, Midgley Angela, Harris David, Richards Ella, Burgess Sarah, Beresford Michael W
Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
Pediatr Rheumatol Online J. 2015 Apr 10;13:10. doi: 10.1186/s12969-015-0007-y. eCollection 2015.
The TAM-receptor tyrosine kinase family, Tyro3, Axl and Mer are key to apoptotic cell clearance. Reduced phagocytic clearance in systemic lupus erythematosus (SLE) leads to prolonged exposure of nuclear autoantigen to the immune system. Here we measure the levels of TAM receptors and the phagocytic capacity of monocytes and macrophages in juvenile-onset SLE (JSLE).
Mer protein was measured on monocytes from JSLE, healthy control and JIA patients. JSLE, healthy control and JIA patients' plasma were analysed for soluble Mer (sMer), soluble Tyro3 (sTyro) and soluble Axl (sAxl). A phagocytosis assay measured the effect of JSLE serum on phagocytic potential of JSLE and control monocytes to engulf E. Coli bacteria and healthy macrophages to engulf apoptotic neutrophils.
Mer receptor expression was significantly decreased on JSLE monocytes compared to healthy controls. Plasma sMer, sTyro and sAxl were significantly increased in JSLE patients compared to controls (p < 0.05). Adult healthy control macrophages had significantly decreased phagocytosis of E. Coli and apoptotic neutrophils in the presence of 10% JSLE serum compared to control serum (p < 0.05).
JSLE patients have a decreased phagocytosis due to both serum and cell-derived factors. Significantly increased levels of sMer, sTyro3 and sAxl may be important factors contributing to the deficit in phagocytosis ability.
TAM 受体酪氨酸激酶家族,即 Tyro3、Axl 和 Mer,对凋亡细胞清除至关重要。系统性红斑狼疮(SLE)中吞噬清除功能降低导致核自身抗原长时间暴露于免疫系统。在此,我们检测青少年起病型 SLE(JSLE)中 TAM 受体水平以及单核细胞和巨噬细胞的吞噬能力。
检测 JSLE 患者、健康对照者和幼年特发性关节炎(JIA)患者单核细胞上的 Mer 蛋白。分析 JSLE 患者、健康对照者和 JIA 患者血浆中的可溶性 Mer(sMer)、可溶性 Tyro3(sTyro)和可溶性 Axl(sAxl)。吞噬试验检测 JSLE 血清对 JSLE 和对照单核细胞吞噬大肠杆菌的吞噬潜能以及健康巨噬细胞吞噬凋亡中性粒细胞的影响。
与健康对照相比,JSLE 患者单核细胞上的 Mer 受体表达显著降低。与对照组相比,JSLE 患者血浆中的 sMer、sTyro 和 sAxl 显著升高(p < 0.05)。与对照血清相比,在 10% JSLE 血清存在的情况下,成年健康对照巨噬细胞对大肠杆菌和凋亡中性粒细胞的吞噬作用显著降低(p < 0.05)。
JSLE 患者由于血清和细胞源性因素导致吞噬作用降低。sMer、sTyro3 和 sAxl 水平显著升高可能是导致吞噬能力缺陷的重要因素。