Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus
| Autor: | Daniel T. Eitzman, Hui Wang, Jason S. Knight, Kyle Kleiman, Jintao Wang, Chiao Guo, Jeffrey B. Hodgin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lupus nephritis Infarction Kidney Article Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Lupus Erythematosus Systemic Mice Knockout Membrane Glycoproteins Multidisciplinary Lupus erythematosus Systemic lupus erythematosus integumentary system Terpenes business.industry Cerebral infarction Macrophages Brain Infarction Middle Cerebral Artery medicine.disease Lupus Nephritis Specific Pathogen-Free Organisms Mice Inbred C57BL Stroke CXCL1 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neutrophil Infiltration Antibodies Antinuclear Immunology Female Inflammation Mediators business Nephritis 030215 immunology |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep28997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|