Effect of CXCR2 Inhibition on Behavioral Outcomes and Pathology in Rat Model of Neuromyelitis Optica

Melina Jones, Michael Levy

Research output: Contribution to journalArticle

Abstract

Objective: To reduce immune-mediated damage in a rat model of neuromyelitis optica (NMO) by blocking neutrophil migration using SCH527123, a drug that inhibits CXCR2. Background: Neuromyelitis optica is a relapsing autoimmune disease that preferentially targets the optic nerves and spinal cord leading to blindness and paralysis. Part of the immunopathogenesis of this disease is thought to involve neutrophils, which are present within NMO lesions. We tested the effect of blocking neutrophil migration in an NMO rat model. Methods: The Lewis rat model of NMO uses a myelin-reactive experimental autoimmune encephalomyelitis (EAE) background with passive transfer of pooled human antibody from patients with aquaporin-4 (AQP4) seropositive NMO at onset of EAE symptoms. We treated rats early in the course of EAE with CXCR2 inhibitor and assessed the extent of neutrophil infiltration into the spinal cord and the extent of AQP4 depletion. Results: CXCR2 inhibitor decreased neutrophil migration into the spinal cord of AQP4 IgG-treated EAE rats. However, there was no difference in the acute behavioral signs of EAE or the extent and distribution of AQP4 lesions. This suggests that neutrophils are not centrally involved in the immunopathogenesis of the Lewis rat NMO disease model. Conclusions: CXCR2 inhibitor blocks neutrophil migration into the spinal cord during EAE but does not significantly reduce inflammation or AQP4 lesions in the Lewis rat model of NMO.

Original languageEnglish (US)
Number of pages1
JournalJournal of Immunology Research
Volume2018
DOIs
StatePublished - Jan 1 2018

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Neuromyelitis Optica
Autoimmune Experimental Encephalomyelitis
Aquaporin 4
Pathology
Neutrophils
Spinal Cord
Neutrophil Infiltration
Blindness
Optic Nerve
Myelin Sheath
Paralysis
Autoimmune Diseases
Immunoglobulin G
Inflammation
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Effect of CXCR2 Inhibition on Behavioral Outcomes and Pathology in Rat Model of Neuromyelitis Optica. / Jones, Melina; Levy, Michael.

In: Journal of Immunology Research, Vol. 2018, 01.01.2018.

Research output: Contribution to journalArticle

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