Expression of the murine complement regulatory protein Crry by glial cells and neurons

Davoust, Nathalie; Nataf, Serge; Holers, V. Michael; Barnum, Scott R.

doi:10.1002/(sici)1098-1136(199908)27:2<162::aid-glia6>3.0.co;2-k

Cited by 21 publications

(14 citation statements)

References 32 publications

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“…To study the role of the complement system in microglial priming, we used a mouse strain that lacks a major regulator of the complement cascade, Crry, strongly expressed by microglia (10). Crry regulates the C3 convertase enzymes in rodents (11).…”

Section: Resultsmentioning

confidence: 99%

C3-dependent mechanism of microglial priming relevant to multiple sclerosis

Ramaglia¹,

Hughes²,

Donev³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

133

102

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Microglial priming predisposes the brain to neurodegeneration and affects disease progression. The signal to switch from the quiescent to the primed state is unknown. We show that deleting the C3 convertase regulator complement receptor 1-related protein y (Crry) induces microglial priming. Mice that were double-knockout for Crry and either C3 or factor B did not show priming, demonstrating dependence on alternative pathway activation. Colocalization of C3b/ iC3b and CR3 implicated the CR3/iC3b interaction in priming. Systemic lipopolysaccharide challenge overactivated primed microglia with florid expression of proinflammatory molecules, which were blocked by complement inhibition. Relevance for neurodegenerative disease is exemplified by human multiple sclerosis (MS) and by experimental autoimmune encephalomyelitis (EAE), a model of MS. In human MS, microglial priming was evident in perilesional white matter, in close proximity to C3b/iC3b deposits. EAE was accelerated and exacerbated in Crry-deficient mice, and was dependent on C activation. In summary, C3-dependent microglial priming confers susceptibility to other challenges. Our observations are relevant to progression in MS and other neurological diseases exacerbated by acute insults.

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Section: Resultsmentioning

confidence: 99%

C3-dependent mechanism of microglial priming relevant to multiple sclerosis

Ramaglia¹,

Hughes²,

Donev³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

133

102

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“…The role of complement activation in EAE has been hotly debated over the years (53)(54)(55). Loss of C3 apparently attenuates EAE (56), and expression of the complement inhibitor sCrry prevents EAE (57). Also, complement activation appears to be crucial in the context of EAE exacerbated by the inoculation of demyelinating Abs (39,40,58,59).…”

Section: Discussionmentioning

confidence: 99%

Autoantibody-mediated demyelination depends on complement activation but not activatory Fc-receptors

Urich

Gutcher

Prinz

2006

Proc. Natl. Acad. Sci. U.S.A.

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The precise mechanisms leading to CNS inflammation and myelin destruction in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) remain the subject of intense debate. In both MS and EAE, autoantibodies (autoAbs) are thought to be involved in tissue destruction through recruiting Fc receptor (FcR)-bearing cells or direct cytotoxic effects through the activation of the complement pathway. Whereas intrathecal immunoglobulin (Ig) production and Ig deposition in inflammatory lesions is a hallmark of MS, mice deficient in B cells and Igs develop severe EAE. Paradoxically, mice of the same genetic background but deficient in FcR␥ are EAE-resistant. We found that the functional expression of FcR␥ on systemic accessory cells, but not CNS-resident cells, appears to be vital for the development of CNS inflammation, independent of antigenpresenting cell function or Ab involvement. On the other hand, we found that the injection of antimyelin oligodendrocyte glycoproteinAbs drastically worsens disease severity, inflammation, and demyelination. Using FcR␥ ؊/؊ and C1q ؊/؊ mice, we could definitively establish that the demyelinating capacity of such autoAb in vivo relies entirely on complement activation and is FcR-independent.autoimmunity ͉ multiple sclerosis ͉ neuropathology ͉ B cells ͉ humoral immunity

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“…Of 38 significantly regulated genes in this category, 34 of these were upregulated in expression. Predominant in this class were all 43,44 Many of these messages are associated with the activation of microglia, and markers for activated microglia have been identified in the pressure-injured ONH. 45,46 In activated microglia, the upregulation of ionized calcium-binding adaptor molecule 1 (IBA1), also known as allograft inflammatory factor 1, is associated with the formation of lamellipodia and membrane ruffles.…”

Section: Effect Of Elevated Iop On Onh Expression Of Immune Response mentioning

confidence: 99%

Global Changes in Optic Nerve Head Gene Expression after Exposure to Elevated Intraocular Pressure in a Rat Glaucoma Model

Johnson

Jia

Cepurna

et al. 2007

Invest. Ophthalmol. Vis. Sci.

236

222

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Expression of the murine complement regulatory protein Crry by glial cells and neurons

Cited by 21 publications

References 32 publications

C3-dependent mechanism of microglial priming relevant to multiple sclerosis

C3-dependent mechanism of microglial priming relevant to multiple sclerosis

Autoantibody-mediated demyelination depends on complement activation but not activatory Fc-receptors

Global Changes in Optic Nerve Head Gene Expression after Exposure to Elevated Intraocular Pressure in a Rat Glaucoma Model

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