Effects of Complement C5 on Apoptosis in Experimental Autoimmune Encephalomyelitis

Niculescu, Teodora; Weerth, Susanna; Niculescu, Florin; Cudrici, Cornelia; Rus, Violeta; Raine, Cedric S.; Shin, Moon L.; Rus, Horea

doi:10.4049/jimmunol.172.9.5702

Cited by 42 publications

(44 citation statements)

References 34 publications

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“…During recovery, however, C5-s mice showed significantly fewer apoptotic cells than C5-d mice. In addition, although both mouse groups displayed TUNEL-positive OLGs, C5-s mice had significantly fewer TUNEL-positive OLGs than C5-d mice during both acute EAE and recovery phases [65]. These findings are consistent with the role of C5 in protecting OLG from apoptosis in EAE, possibly by forming C5b-9 and promoting remyelination during recovery.…”

Section: Dual Role Of C5b-9 In Vivo: Proinflammatory Demyelination Ansupporting

confidence: 78%

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Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

Cudrici

Niculescu²,

Niculescu³

et al. 2006

JRRD

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Abstract-Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It is mediated by activated lymphocytes, macrophages, microglia, and complement. In MS, myelin-forming oligodendrocytes (OLGs) are the targets of inflammatory and immune attacks. OLG death by apoptosis or necrosis causes the cell loss seen in MS plaques. Studies of experimental allergic encephalomyelitis (EAE) in caspase 11-deficient mice show that caspasemediated death of OLGs is critical to demyelination. Complement activation may affect MS pathogenesis through activated terminal complex C5b-9, which promotes demyelination, and through sublytic C5b-9, which protects OLGs from apoptosis. By inducing EAE in C5-deficient mice, we showed that complement C5 promotes axon preservation and new myelin formation, which protect OLGs from apoptosis. These findings indicate that activated complement C5b-9 plays a proinflammatory role in acute MS but may also protect OLGs from death in chronic MS.

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Section: Dual Role Of C5b-9 In Vivo: Proinflammatory Demyelination Ansupporting

confidence: 78%

“…On the other hand, C5-sufficient (C5-s) mice showed prominent myelin repair and axon preservation during the chronic phase of EAE. We also analyzed the effect of C5 on OLG apoptosis during EAE in C5-d mice [65]. In acute EAE, C5-d and C5-s mice had similar numbers of total apoptotic cells.…”

Section: Dual Role Of C5b-9 In Vivo: Proinflammatory Demyelination Anmentioning

confidence: 99%

Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

Cudrici

Niculescu²,

Niculescu³

et al. 2006

JRRD

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“…C5-sufficient mice subjected to experimental autoimmune encephalomyelitis had far fewer apoptotic cells during recovery compared with C5-deficient mice (85), raising the possibility that the chronic regenerative effects of C5 outweigh its acute proinflammatory damages. C5 seems to partially mediate its effects through gene regulation of insulin-like growth factors (IGF), their binding proteins (IGFBP), and TGF-β3 (75).…”

Section: Complement Proteins Exert Prosurvival and Antiapoptotic Effectsmentioning

confidence: 99%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

229

249

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Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

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“…A similar indirect immunoperoxidase technique was used for CD3, CD4, CD8, CD68, and CD83 staining. For staining of OLG/myelin using mouse monoclonal MAB 328 (Chemicon, Temacula, CA) the cryostat sections incubated overnight at 4°C with the MAB 328 (1:10,000) in 0.1% Tween-PBS as previously described (Niculescu et al, 2004). The sections were washed several times in PBS, reacted with anti-mouse biotinylated secondary antibody (1:250) in PBS, and then with avidin-biotin-peroxidase complex (Vector Labs).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Cudrici

Ito

Zafranskaia

et al. 2007

Experimental and Molecular Pathology

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We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for inflammatory cells (CD68, CD8, CD4, CD3, CCR7, CCR5). We found cells expressing CD209 and containing myelin basic protein in both perivascular and parenchymal areas of NLGM. Our findings showing the expression of CD209 + cells in NLGM parenchymal areas are surprising relative to the previous literature which reported the presence of CD209 + DCs only in MS plaque perivascular areas. Although less numerous than CD209 + cells, NLGM cells expressing mature DCs marker CD205 were consistently detected in perivascular cuffs of most lesions. In double labeling experiments, some but not all of the CD209 + cells also expressed CD68 and CCR5. We also found CD209 + cells in close contact with CD3 + lymphocytes suggesting that DCs might contribute to the local activation of pathogenic T cells in the NLGM. Since injury to the NLGM is one of the key factors associated with disability accumulation, targeting DCs may represent a possible new therapeutic approach in MS to prevent disease progression.

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Effects of Complement C5 on Apoptosis in Experimental Autoimmune Encephalomyelitis

Cited by 42 publications

References 34 publications

Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

Cancer and the Complement Cascade

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

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