Cytosolic phospholipase A2α-deficient mice are resistant to experimental autoimmune encephalomyelitis

130Citations
Citations of this article
64Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is a model of human multiple sclerosis. Cytosolic phospholipase A2α(cPLA 2α), which initiates production of prostaglandins, leukotrienes, and platelet-activating factor, is present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well as an adoptive transfer model, we showed that cPLA2α-/- mice are resistant to EAE. Histologic examination of the CNS from MOG-immunized mice revealed extensive inflammatory lesions in the cPLA2α +/- mice, whereas the lesions in cPLA2α +/- mice were reduced greatly or completely absent. MOG-specific T cells generated from WT mice induced less severe EAE in cPLA2α -/- mice compared with cPLA2α+/- mice, which indicates that cPLA2α plays a role in the effector phase of EAE. Additionally, MOG-specific T cells from cPLA2α -/- mice, transferred into WT mice, induced EAE with delayed onset and lower severity compared with EAE that was induced by control cells; this indicates that cPLA2α also plays a role in the induction phase of EAE. MOG-specific T cells from cPLA2α+/- mice were deficient in production of Th1-type cytokines. Consistent with this deficiency, in vivo administration of IL-12 rendered cPLA2α -/- mice susceptible to EAE. Our data indicate that cPLA 2α plays an important role in EAE development and facilitates differentiation of T cells toward the Th1 phenotype. JEM © The Rockefeller University Press.

Cite

CITATION STYLE

APA

Marusic, S., Leach, M. W., Pelker, J. W., Azoitei, M. L., Uozumi, N., Cui, J., … Clark, J. D. (2005). Cytosolic phospholipase A2α-deficient mice are resistant to experimental autoimmune encephalomyelitis. Journal of Experimental Medicine, 202(6), 841–851. https://doi.org/10.1084/jem.20050665

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free