title: Altered cell-cell and cell-matrix interactions in the development of systemic autoimmunity.
abstract: MPhi of mice from the major inbred models of systemic lupus erythematosus (SLE) have an identical defect affecting the activity of the cytoskeletal regulator and G-protein Rho. This abnormality is triggered by apo cells. Strikingly, SLE-prone MPhi show normal Rho activity when cultured in the absence of apo cells. We used gene arrays to identify adhesion-related gene products that are abnormally expressed by MPhi from prediseased 4-6-week-old SLE-prone MRL mice in the presence of serum lipids mimicking apo cells (SL-Apo). MPhi of MRL mice differentially expressed 42 adhesion-related genes in the presence of SL-Apo. Of these, 32 were expressed normally in the absence of SL-Apo. As adhesive interactions play a major role in lymphocyte activation, the detected apo cell-dependent abnormality could predispose to the development of autoimmunity. Indeed, several recent genetic studies support a role for adhesion-related genes in the pathogenesis of chronic autoimmunity.
authors.affiliation: Department of Biology, Kutztown University of Pennsylvania, Kutztown, PA 19530, USA. antoni@kutztown.edu
authors.forename: Angelika
authors.initials: A
authors.lastname: Antoni
authors.forename: Lee H
authors.initials: LH
authors.lastname: Graham
authors.forename: Joyce
authors.initials: J
authors.lastname: Rauch
authors.forename: Jerrold S
authors.initials: JS
authors.lastname: Levine
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion / Q000235:genetics*; D002450:Cell Communication / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology*; D015870:Gene Expression; D008055:Lipids / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D008055:Lipids