Linked Life Data

15699172

Source:http://linkedlifedata.com/resource/pubmed/id/15699172

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-8
pubmed:abstractText
There is compelling evidence that a unique innate immune response in the CNS plays a critical role in host defense and clearance of toxic cell debris. Although complement has been implicated in neuronal impairment, axonal loss, and demyelination, some preliminary evidence suggests that the initial insult consequently activates surrounding cells to signal neuroprotective activities. Using two different models of experimental autoimmune encephalomyelitis, we herein demonstrate selective C1q complement activation on neuron cell bodies and axons. Interestingly, in brains with chronic but not acute experimental autoimmune encephalomyelitis, C3b opsonization of neuronal cell bodies and axons was consistently associated with robust neuronal expression of one of the most effective complement regulators, decay-accelerating factor (CD55). In contrast, levels of other complement inhibitors, complement receptor 1 (CD35), membrane cofactor protein (CD46), and CD59 were largely unaffected on neurons and reactive glial cells in both conditions. In vitro, we found that proinflammatory stimuli (cytokines and sublytic doses of complement) failed to up-regulate CD55 expression on cultured IMR32 neuronal cells. Interestingly, overexpression of GPI-anchored CD55 on IMR32 was capable of modulating raft-associated protein kinase activities without affecting MAPK activities and neuronal apoptosis. Critically, ectopic expression of decay-accelerating factor conferred strong protection of neurons against complement attack (opsonization and lysis). We conclude that increased CD55 expression by neurons may represent a key protective signaling mechanism mobilized by brain cells to withstand complement activation and to survive within an inflammatory site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2353-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15699172-Acute Disease, pubmed-meshheading:15699172-Animals, pubmed-meshheading:15699172-Antigens, CD, pubmed-meshheading:15699172-Antigens, CD46, pubmed-meshheading:15699172-Antigens, CD55, pubmed-meshheading:15699172-Antigens, CD59, pubmed-meshheading:15699172-Apoptosis, pubmed-meshheading:15699172-Axons, pubmed-meshheading:15699172-Brain, pubmed-meshheading:15699172-Callithrix, pubmed-meshheading:15699172-Cell Line, pubmed-meshheading:15699172-Cell Line, Tumor, pubmed-meshheading:15699172-Cell Movement, pubmed-meshheading:15699172-Chronic Disease, pubmed-meshheading:15699172-Complement Hemolytic Activity Assay, pubmed-meshheading:15699172-Complement Pathway, Classical, pubmed-meshheading:15699172-Encephalomyelitis, Autoimmune, Experimental, pubmed-meshheading:15699172-Glycosylphosphatidylinositols, pubmed-meshheading:15699172-Humans, pubmed-meshheading:15699172-K562 Cells, pubmed-meshheading:15699172-Macaca fascicularis, pubmed-meshheading:15699172-Membrane Glycoproteins, pubmed-meshheading:15699172-Membrane Microdomains, pubmed-meshheading:15699172-Neurons, pubmed-meshheading:15699172-Opsonin Proteins, pubmed-meshheading:15699172-Receptors, Complement 3b, pubmed-meshheading:15699172-Signal Transduction, pubmed-meshheading:15699172-U937 Cells
pubmed:year
2005
pubmed:articleTitle
Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation.
pubmed:affiliation
Brain Inflammation Immunity Group (BIIG), Cardiff University, Cardiff, United Kingdom. jvbe@lundbeck.com
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't