The C5a complement activation peptide increases IL-1β and IL-6 release from amyloid-β primed human monocytes: implications for Alzheimer’s disease

O’Barr, Stephen A.; Cooper, Neil R.

doi:10.1016/s0165-5728(00)00291-5

Cited by 62 publications

(41 citation statements)

References 42 publications

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“…Activation of the classical complement pathway by binding of C1q to fibrillar A␤ can result in generation of chemotactic molecules that would recruit astrocytes and microglia to the area of the plaque (Yao et al, 1990;Gasque et al, 1997;O'Barr and Cooper, 2000). To assess the role of C1q and the classical complement pathway in this glial response, we compared astrocytic and microglial reactivity in APP and APPQϪ/Ϫ mice.…”

Section: Less Glial Activation Is Seen In the Proximity Of Fibrillar mentioning

confidence: 99%

“…In AD brain, C1q has been shown to be associated with fibrillar A␤ plaques and activated glia (Afagh et al, 1996). Other complement proteins were also detected in the plaque area, and their synthesis has been shown to occur within the AD brain (Johnson et al, 1992;Shen et al, 1997) Previously published evidence suggests that complement activation occurs in vivo and through the recruitment of activated glia (Yao et al, 1990;O'Barr and Cooper, 2000) can initiate an inflammatory reaction near the plaque that could lead to enhanced neurodegeneration (Benveniste et al, 2001;Tenner and Webster, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

Fonseca¹,

Zhou²,

Botto³

et al. 2004

J. Neurosci.

287

248

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C1q, the recognition component of the classical complement activation pathway, is a multifunctional protein known to be expressed in brain of Alzheimer's disease (AD) patients. To experimentally address the role of C1q in AD, a mouse model lacking C1q (APPQϪ/Ϫ) was generated by crossing Tg2576 animals (APP) with C1q-deficient mice. The pathology of APPQϪ/Ϫ was compared with that of APP mice and B6SJL controls at 3-16 months of age by immunohistochemistry and Western blot analysis. At younger ages (3-6 months), when no plaque pathology was present, no significant differences were seen in any of the neuronal or glial markers tested. At older ages (9 -16 months), the APP and APPQϪ/Ϫ mice developed comparable total amyloid and fibrillar ␤-amyloid in frontal cortex and hippocampus; however, the level of activated glia surrounding the plaques was significantly lower in the APPQϪ/Ϫ mice at 12 and 16 months. In addition, although Tg2576 mice showed a progressive decrease in synaptophysin and MAP2 in the CA3 area of hippocampus compared with control B6SJL at 9, 12, and 16 months, the APPQϪ/Ϫ mice had significantly less of a decrease in these markers at 12 and 16 months. In a second murine model for AD containing transgenes for both APP and mutant presenilin 1 (APP/PS1), a similar reduction of pathology was seen in the APPPS1QϪ/Ϫ mice. These data suggest that at ages when the fibrillar plaque pathology is present, C1q exerts a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation.

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Section: Less Glial Activation Is Seen In the Proximity Of Fibrillar mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

Fonseca¹,

Zhou²,

Botto³

et al. 2004

J. Neurosci.

287

248

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“…C5a exerts these activities by binding to G-protein-coupled C5a receptor (C5aR) 1 on the plasma membrane of target cells (3). These biological activities of C5a are implicated in a variety of diseases such as rheumatoid arthritis (4,5), systemic lupus erythematosus (6 -9), reperfusion injury (10), Alzheimer's disease (11)(12)(13)(14)(15), and sepsis (16,17). The pathogenic action of C5/C5a is also shown in some animal models.…”

Section: ؉mentioning

confidence: 99%

Identification of a Potent and Orally Active Non-peptide C5a Receptor Antagonist

Sumichika

Sakata

Sato

et al. 2002

Journal of Biological Chemistry

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“…C5a is a major anaphylactic and chemotactic agent and promotes production of cytokines (e.g. IL-1β, IL-6, IL-12) that are actively involved in EAMG pathogenesis (Morgan et al, 1992;O'Barr and Cooper, 2000). Therefore, inborn deficiency of C5a signaling through C5a receptor (C5aR) might be expected to influence EAMG susceptibility.…”

Section: Introductionmentioning

confidence: 99%

C5a is not involved in experimental autoimmune myasthenia gravis pathogenesis

Qi¹,

Tüzün²,

Allman³

et al. 2008

Journal of Neuroimmunology

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C5 deficient mice are highly resistant to experimental autoimmune myasthenia gravis (EAMG) despite intact immune response to acethylcholine receptor (AChR), validating the pivotal role played by membrane attack complex (MAC, C5b-9) in neuromuscular junction destruction. To distinguish the significance of C5a from that of C5b in EAMG pathogenesis, C5a receptor (C5aR) knockout (KO) and wild-type (WT) mice were immunized with AChR to induce pathogenic antiAChR antibodies. In contrast with C5 deficient mice, C5aR KO mice were equally susceptible to EAMG as WT mice and exhibited comparable antibody and lymphocyte proliferation response to AChR implicating that C5a is not involved in EAMG development.

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The C5a complement activation peptide increases IL-1β and IL-6 release from amyloid-β primed human monocytes: implications for Alzheimer’s disease

Cited by 62 publications

References 42 publications

Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

Identification of a Potent and Orally Active Non-peptide C5a Receptor Antagonist

C5a is not involved in experimental autoimmune myasthenia gravis pathogenesis

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