University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, Ann Arbor, Michigan, USA.
University of Michigan, Department of Internal Medicine, Division of Rheumatology, Ann Arbor, Michigan, USA.
Sci Rep. 2016 Jun 30;6:28997. doi: 10.1038/srep28997.
Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1(-/-)) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls. However, stroke size was not increased in pristane-treated Psgl-1(-/-) mice compared to controls, despite evidence of increased nephritis in Psgl-1(-/-) mice. Pristane-treated WT mice showed elevated anti-dsDNA, anti-snRNP, CXCL1, and MCP-1 levels compared to untreated mice; however levels of anti-snRNP, MCP-1, and CXCL1 were reduced in pristane-treated Psgl-1(-/-) mice compared to pristane-treated WT mice. Infiltration of neutrophils and macrophages at the cerebral infarction site were reduced in pristane-treated Psgl-1(-/-) mice compared to pristane-treated WT mice. In conclusion, the increase in stroke size associated with lupus is prevented by Psgl-1 deficiency while nephritis is exacerbated. Therapies targeting Psgl-1 may be useful in the management of SLE patients at high risk of acute vascular complications although elucidation of downstream pathways will be necessary to identify targets that do not promote nephritis.
系统性红斑狼疮（SLE）与血管并发症的风险升高有关，包括中风。针对白细胞募集的治疗方法可能有益于减少与 SLE 相关的血管并发症。采用 pristane 在雌性野生型（WT）和 P 选择素糖蛋白配体-1 缺陷（Psgl-1(-/-)）小鼠中诱导狼疮。采用光化学损伤大脑中动脉（MCA）诱导中风。与非 pristane 处理的 WT 对照相比，经 pristane 处理的 WT 小鼠中风面积增加。然而，与对照相比，经 pristane 处理的 Psgl-1(-/-)小鼠中风面积没有增加，尽管 Psgl-1(-/-)小鼠肾炎增加。与未处理的小鼠相比，经 pristane 处理的 WT 小鼠显示出更高的抗 dsDNA、抗 snRNP、CXCL1 和 MCP-1 水平；然而，与经 pristane 处理的 WT 小鼠相比，经 pristane 处理的 Psgl-1(-/-)小鼠的抗 snRNP、MCP-1 和 CXCL1 水平降低。与经 pristane 处理的 WT 小鼠相比，经 pristane 处理的 Psgl-1(-/-)小鼠在脑梗死部位的中性粒细胞和巨噬细胞浸润减少。结论：Psgl-1 缺乏可预防狼疮相关中风面积增加，而肾炎加重。尽管需要阐明下游途径以确定不促进肾炎的靶点，但针对 Psgl-1 的治疗可能对有急性血管并发症高风险的 SLE 患者有用。
