Complement C1qB and C4 mRNAs responses to lesioning in rat brain

Pasinetti, Giulio Maria; Johnson, Steven A.; Rozovsky, Irina; Lampert-Etchells, Martha; Morgan, David; Gordon, Marcia N.; Morgan, Todd E.; Willoughby, David A.; Finch, Caleb E.

doi:10.1016/0014-4886(92)90028-o

Cited by 129 publications

(42 citation statements)

References 49 publications

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“…We found that constitutive and lesion-induced C1q biosynthesis was absent in any brain-resident cells other than cells of the microglia/ macrophage lineage. This conforms to other reports of experimental brain lesions in vivo (22,39) and to in vitro data (28,29) providing strong evidence for microglial biosynthesis of C1q.…”

Section: Discussionsupporting

confidence: 92%

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Schäfer

Schwaeble

Post

et al. 2000

The Journal of Immunology

150

108

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Recent evidence suggests that the pathophysiology of neurodegenerative and inflammatory neurological diseases has a neuroimmunological component involving complement, an innate humoral immune defense system. The present study demonstrates the effects of experimentally induced global ischemia on the biosynthesis of C1q, the recognition subcomponent of the classical complement activation pathway, in the CNS. Using semiquantitative in situ hybridization, immunohistochemistry, and confocal laser scanning microscopy, a dramatic and widespread increase of C1q biosynthesis in rat brain microglia (but not in astrocytes or neurons) within 24 h after the ischemic insult was observed. A marked increase of C1q functional activity in cerebrospinal fluid taken 1, 24, and 72 h after the ischemic insult was determined by C1q-dependent hemolytic assay. In the light of the well-established role of complement and complement activation products in the initiation and maintenance of inflammation, the ischemia-induced increase of cerebral C1q biosynthesis and of C1q functional activity in the cerebrospinal fluid implies that the proinflammatory activities of locally produced complement are likely to contribute to the pathophysiology of cerebral ischemia. Pharmacological modulation of complement activation in the brain may be a therapeutic target in the treatment of stroke.

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Section: Discussionsupporting

confidence: 92%

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Schäfer

Schwaeble

Post

et al. 2000

The Journal of Immunology

150

108

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“…Johnson and colleagues (1992) and Pasinetti and colleagues (1992) demonstrated the expression of C4 by pyramidal neurons as determined by co-localization studies using antibody to neuron-specific enolase. Clq expression was localized in these studies to CR3-positive microglia and was also detected in primary rat neuron cultures Pasinetti et al, 1992). In other studies, Walker and McGeer (1992) detected Clq, C3, and C4 mRNA in postmortem normal and Alzheimer's brains; however, no co-localization studies were performed.…”

Section: Cns Synthesis Of Complement Activation and Terminal Componentsmentioning

confidence: 58%

“…Nevertheless, these studies collectively suggest that the CNS has the capability of mounting a complement-mediated response through both activation pathways (and possibly through the terminal pathway) just as other tissues and organ systems outside the CNS. Aside from astrocytes, microglia, neurons, and cells in the hippocampus have been shown to express mRNA for several complement activation components, including Clq, C3, C4 (Rozenmuller et al, 1990;Johnson et al, 1992;Pasinetti et al, 1992;Walker and McGeer, 1992). In addition, Rozemuller and colleagues (1990) demonstrated the presence of Clq and C3 activation peptides and the acute phase protein, oCj-antichymotrypsin, in the cerebral cortex and hippocampus.…”

Section: Cns Synthesis Of Complement Activation and Terminal Componentsmentioning

confidence: 99%

Complement Biosynthesis in the Central Nervous System

Barnum

1995

Critical Reviews in Oral Biology & Medicine

187

103

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ABSTRACT:Complement is an important effector arm of the human immune response. Binding of proteolytic fragments derived from activation of complement by specific receptors leads to responses as diverse as inflammation, opsonization, and B-cell activation. The importance of characterizing the expression and regulation of complement in the CNS is highlighted by growing evidence that complement plays a significant role in the pathogenesis of a variety of neurological diseases, such as multiple sclerosis and Alzheimer's disease. \n vitro studies have demonstrated that astrocytes, the predominant glial cell type in the brain, are capable of expressing or producing a majority of the components of the complement system. Expression of many complement proteins synthesized by astrocytes is regulated by both pro-and anti-inflammatory cytokines, many of which are also produced by several cell types in the CNS. In addition to astrocytes, ependymal cells, endothelial cells, microglia, and neurons have recently been shown to synthesize various complement proteins or express complement receptors on their cell surfaces. Together, these studies demonstrate that several cell types throughout the brain have the potential to express complement and, in many cases, increase expression in response to mediators of the acute phase response. These studies suggest that complement may play a greater role in CNS immune responses than previously thought, and pave the way for better understanding of the dynamics of complement expression and regulation in vivo. Such understanding may lead to therapeutic manipulation of complement host defense functions in a variety of inflammatory and degenerative diseases in the CNS.

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“…It is noteworthy that many cells of the central nervous system are more susceptible to a complement attack, since they lack important complement regulators such as CD59 (84). Complement products were demonstrated to be dramatically upregulated in models of cerebral ischemia in rats (85), and evidence for deposition of C3d and C9 after experimental cerebral contusion was found (86). In agreement with these experimental findings, systemic complement activation has been shown in stroke patients (87).…”

Section: Traumatic Brain Injurymentioning

confidence: 60%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

190

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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Complement C1qB and C4 mRNAs responses to lesioning in rat brain

Cited by 129 publications

References 49 publications

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Complement Biosynthesis in the Central Nervous System

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

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