Characterization of neuronal cell death induced by complement activation

Shen, Yong; Halperin, José A.; Benzaquen, Laura R.; Lee, Chi-Ming

doi:10.1016/s1385-299x(96)00026-8

Cited by 22 publications

(13 citation statements)

References 16 publications

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“…One possible explanation is that complement activation affects WNV CNS entry by lysing infected peripheral neurons. Complement is synthesized by several different types of neurons (4), and its activation has been recently shown to cause neuronal cell death through the formation of the membrane attack complex (56,57). Alternatively, complement activation could trigger a distinct cytokine expression pattern during the initial phases of infection.…”

Section: Discussionmentioning

confidence: 99%

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Mehlhop

Whitby²,

Oliphant

et al. 2005

J Virol

144

134

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Infection with West Nile virus (WNV) causes a severe infection of the central nervous system (CNS) with higher levels of morbidity and mortality in the elderly and the immunocompromised. Experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. Here, we demonstrate that the complement system, a major component of innate immunity, controls WNV infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in solution and lysing WNV-infected cells. More decisively, mice that genetically lack the third component of complement or complement receptor 1 (CR1) and CR2 developed increased CNS virus burdens and were vulnerable to lethal infection at a low dose of WNV. Both C3-deficient and CR1-and CR2-deficient mice also had significant deficits in their humoral responses after infection with markedly reduced levels of specific anti-WNV immunoglobulin M (IgM) and IgG. Overall, these results suggest that complement controls WNV infection, in part through its ability to induce a protective antibody response.

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Section: Discussionmentioning

confidence: 99%

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Mehlhop

Whitby²,

Oliphant

et al. 2005

J Virol

144

134

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“…The overall effect of complement activation in AD depends on the balance of its detrimental and beneficial effects. On one side, complement activation could induce cell lysis and cause cell death (Shen et al, 1997; Fonseca et al, 2004); on the other side, complement components such as C1q and C3b can promote the clearance of cellular debris and apoptotic cells and enhance cell survival (Wyss-Coray et al, 2002; Rus et al, 2006). The immunohistochemical localization of the MAC was also demonstrated in Pick's Disease where Pick bodies were stained intensely for the MAC (Yasuhara et al, 1994).…”

Section: Complement In the Brainmentioning

confidence: 99%

Neuroprotection in stroke by complement inhibition and immunoglobulin therapy

et al. 2009

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Activation of the complement system occurs in a variety of neuroinflammatory diseases and neurodegenerative processes of the CNS. Studies in the last decade have demonstrated that essentially all of the activation components and receptors of the complement system are produced by astrocytes, microglia, and neurons. There is also rapidly growing evidence to indicate an active role of the complement system in cerebral ischemic injury. In addition to direct cell damage, regional cerebral ischemia and reperfusion (I/R) induces an inflammatory response involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b. The use of specific inhibitors to block complement activation or their mediators such as C5a, can reduce local tissue injury after I/R. Consistent with therapeutic approaches that have been successful in models of autoimmune disorders, many of the same complement inhibition strategies are proving effective in animal models of cerebral I/R injury. One new form of therapy, which is less specific in its targeting of complement than monodrug administration, is the use of immunoglobulins. Intravenous immunoglobulin (IVIG) has the potential to inhibit multiple components of inflammation, including complement fragments, pro-inflammatory cytokine production and leukocyte cell adhesion. Thus, IVIG may directly protect neurons, reduce activation of intrinsic inflammatory cells (microglia) and inhibit transendothelial infiltration of leukocytes into the brain parenchyma following an ischemic stroke. The striking neuroprotective actions of IVIG in animal models of ischemic stroke suggest a potential therapeutic potential that merits consideration for clinical trials in stroke patients.

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“…MAC induces concentration‐dependent neuronal cell death and changes in membrane permeability to Na + , K + and Ca 2+ , release of cytokines, eicosanoids, and reactive‐free radicals. These changes occur at sublytic concentrations of MAC 23. MAC is also responsible for the demyelination of neurons in demyelinated forms of certain disorders 24…”

Section: The Complement System In Neurodegenerationmentioning

confidence: 99%

Herbal Complement Inhibitors in the Treatment of Neuroinflammation: Future Strategy for Neuroprotection

Kulkarni

Kellaway

Kotwal

2005

Annals of the New York Academy of Sciences

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The upregulated complement system plays a damaging role in disorders of the central nervous system (CNS). The classical and alternate pathways are two major pathways activated in neuroinflammatory disorders such as Alzheimer's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, HIV-associated dementia, Parkinson's disease, and mad cow disease. Failure of currently available anti-inflammatory agents, especially cyclooxygenase inhibitors, in offering significant neuroprotection in large epidemiologic clinical trials of CNS disorders suggests an urgent need for the development of new neuroprotective agents. The positive preclinical outcomes in treating CNS disorders by complement regulatory molecules, such as vaccinia virus complement control protein, suggest the possibility of using complement-inhibitory molecules as neuroprotective agents. Several active ingredients of herbal origin are found to have complement-inhibitory activity. These herbal ingredients along with other anti-inflammatory roles might be useful in treating neuroinflammation associated with CNS disorders. Active ingredients of herbal origin with complement inhibitory ingredients are summarized and classified according to their chemical nature and specificity towards the major pathways activating the complement system. The structure activity relationship of some specific examples is also discussed in this report. This information might be helpful in formulating a natural panacea against complement-mediated neuroinflammation.

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Characterization of neuronal cell death induced by complement activation

Cited by 22 publications

References 16 publications

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Neuroprotection in stroke by complement inhibition and immunoglobulin therapy

Herbal Complement Inhibitors in the Treatment of Neuroinflammation: Future Strategy for Neuroprotection

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