Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment.

Abstract

Autoantibody neuromyelitis optica-IgG (NMO-IgG) recognizing aquaporin-4 (AQP4) is implicated as playing a central role in the physiopathology of NMO. The aim of this in vitro-based study was to characterize functional consequences of interaction between NMO-IgG and cells of the neurovascular unit (astrocytes and brain endothelium) that would provide insight into recognized features of NMO, namely altered blood-brain barrier (BBB) permeability and granulocyte recruitment. We used sera from NMO and longitudinally extensive transverse myelitis cases shown to bind in a characteristic perivascular pattern to primate cerebellar slices. Using flow cytometry, we found that sera from NMO-IgG-positive patients reacted with CNS-derived human fetal astrocytes, whereas sera from multiple sclerosis patients did not. We demonstrated that NMO-IgG binding to astrocytes alters aquaporin-4 polarized expression and increases permeability of a human BBB endothelium/astrocyte barrier. We further demonstrated that NMO-IgG binding to human fetal astrocytes can result in NK cell degranulation, astrocyte killing by Ab-dependent cellular cytotoxicity and complement-dependent granulocyte attraction through the BBB model. Our study highlights important functional roles for NMO-IgG that could account for pathological lesions and BBB dysfunction observed in NMO.

• Authors: Thierry Vincent, Philippe Saikali, Romain Cayrol, Alejandro D Roth, Amit Bar-Or, Alexandre Prat, Jack P Antel
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 8 Pg. 5730-7 (Oct 15 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 18832732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AQP4 protein, human
• Aquaporin 4
• Autoantibodies
• Immunoglobulin G
• Complement System Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Aquaporin 4 (immunology)
• Astrocytes (immunology, pathology)
• Autoantibodies (blood, immunology)
• Blood-Brain Barrier (immunology, pathology)
• Cell Degranulation (immunology)
• Cerebellum (blood supply, immunology, pathology)
• Complement System Proteins (immunology)
• Female
• Fetus (immunology, pathology)
• Granulocytes (immunology, pathology)
• Humans
• Immunity, Cellular (immunology)
• Immunoglobulin G (blood, immunology)
• Killer Cells, Natural (immunology, pathology)
• Male
• Middle Aged
• Multiple Sclerosis (blood, immunology, pathology)
• Neuromyelitis Optica (blood, immunology, pathology)
• Permeability
• Primates