title: Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus.
abstract: 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.
authors.affiliation: University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, Ann Arbor, Michigan, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: University of Michigan, Department of Internal Medicine, Division of Rheumatology, Ann Arbor, Michigan, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Knight
authors.affiliation: University of Michigan, Department of Pathology, Ann Arbor, Michigan, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Hodgin
authors.affiliation: University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, Ann Arbor, Michigan, USA.
authors.forename: Jintao
authors.initials: J
authors.lastname: Wang
authors.affiliation: University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, Ann Arbor, Michigan, USA.
authors.forename: Chiao
authors.initials: C
authors.lastname: Guo
authors.affiliation: University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, Ann Arbor, Michigan, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Kleiman
authors.affiliation: University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, Ann Arbor, Michigan, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D013047:Specific Pathogen-Free Organisms; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013729:Terpenes / Q000633:toxicity
chemical_list: D000974:Antibodies, Antinuclear; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D013729:Terpenes; C009042:pristane