Linked Life Data

16242306

Source:http://linkedlifedata.com/resource/pubmed/id/16242306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-11-21
pubmed:abstractText
A current model for the evolution of systemic lupus erythematosus hypothesizes that there is a genetic predisposition coupled with an environmental or infectious trigger. This study investigated whether apoptotic cells given with a proinflammatory signal could induce features of lupus. Balb/c mice were injected with an apoptotic Balb/c-derived myeloid cell line, J774.1, either with or without the DNA-binding protein HMGB1 for five injections over 16 days in an IACUC approved study. Mice were sacrificed at 6 weeks and 12 weeks after treatment. Renal disease was assessed by immunofluorescence and autoantibodies were defined by ELISA. Western blotting was performed to characterize autoantigens. Mice injected with apoptotic cells developed antibodies to histones, SSA, ssDNA, and phospholipids. Antibodies to SSA and ssDNA persisted; however, antibodies to histones, and phospholipid declined at 12 weeks. IgG deposits in the kidney were detected at 6 weeks and persisted through 12 weeks primarily in animals that received both apoptotic cells and HMGB1. Autoantibodies in mice were diverse but the mice that received apoptotic cells developed particularly high titer antibodies to an unknown 78kDa protein. This protein became externalized on the surface of J774.1 cells in the presence of HMGB1. Mice that received apoptotic J774.1 cells with HMGB1 developed more extensive renal IgG deposition. While the mechanism is uncertain, an important effect of HMGB1 was to alter the subcellular distribution of a major autoantigen, making the autoantigen accessible for immune responses. This is the first description of an inflammatory stimulus altering the immunologic availability of a potential autoantigen.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0896-8411
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
264-71
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Apoptotic cells, autoantibodies, and the role of HMGB1 in the subcellular localization of an autoantigen.
pubmed:affiliation
Division of Allergy and Immunology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural