Complement components of the innate immune system in health and disease in the CNS
Abstract
The innate immune system and notably the complement (C) system play important roles in host defense to recognise and kill deleterious invaders or toxic entities, but activation at inappropriate sites or to an excessive degree can cause severe tissue damage. C has been implicated as a factor in the exacerbation and propagation of tissue injury in numerous diseases including neurodegenerative disorders. In this article, we review the evidence indicating that brain cells can synthesise a full lytic C system and also express specific C inhibitors (to protect from C activation and C lysis) and C receptors (involved in cell activation, chemotaxis and phagocytosis). We also summarise the mechanisms involved in the antibody-independent activation of the classical pathway of C in Alzheimer’s disease, Huntington’s disease and Pick’s disease. Although the primary role of C activation on a target cell is to induce cell lysis (particularly of neurons), we present evidence indicating that C (C3a, C5a, sublytic level of C5b-9) may also be involved in pro- as well as anti-inflammatory activities. Moreover, we discuss evidence suggesting that local C activation may contribute to tissue remodelling activities during repair in the CNS. 0 2000 Elsevier Science B.V. All rights reserved.
Part of CIRS biomarkers research · Curated by Lauren Lowenstein, The Biotoxin Lady
Key Biomarkers
Symptom Clusters
Cited By (14)
- Cytokines and innate inflammation in the pathogenesis of human traumatic brain injuryProgress in Neurobiology · 2011
- Complement C3a receptors in the pituitary gland: a novel pathway by which an innate immune molecule releases hormones involved in the control of inflammationThe FASEB Journal · 2003
- Decay-Accelerating Factor (CD55) Is Expressed by Neurons in Response to Chronic but Not Acute Autoimmune Central Nervous System Inflammation Associated with Complement ActivationThe Journal of Immunology · 2005
- Innate Immunity and Protective Neuroinflammation: New Emphasis on the Role of Neuroimmune Regulatory ProteinsInternational review of neurobiology · 2007
- The complement system is an integrated part of the natural innate immune response in the brainThe FASEB Journal · 2001
- Neuroinvasion by pathogens: a key role of the complement systemMolecular Immunology · 2002
- Impaired volume regulation is the mechanism of excitotoxic sensitization to complementJournal of Neuroscience · 2006
- Activation of Complement in the Central Nervous SystemAnnals of the New York Academy of Sciences · 2003
- Innate immunity and brain inflammation: the key role of complementExpert Reviews in Molecular Medicine · 2003
- Distribution of complement anaphylatoxin receptors and membrane-bound regulators in normal human retinaExperimental Eye Research · 2006
- Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, “protective” glial stem cells and stromal ependymal cellsBrain Research Reviews · 2005
- Complement: a unique innate immune sensor for danger signalsMolecular Immunology · 2004
- Gasque P. “Eat me” and “don’t eat me” signal govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement systemMol Immunol · 2003
- Complement in central nervous system inflammationImmunologic Research · 2002
References (5)
- Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytesThe Journal of Immunology · 1995
- Expression of a functional anaphylatoxin C3a receptor by astrocytesJournal of Neurochemistry · 1998
- The role of complement in disorders of the nervous systemImmunopharmacology · 1997
- Differential regulation of C3 gene expression in human astroglioma cells by interferon-γ and interleukin-1βNeuroscience Letters · 1995
- Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous systemAmerican Journal Of Pathology · 1997
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