title: Serum soluble MD-1 levels increase with disease progression in autoimmune prone MRL(lpr/lpr) mice.
abstract: MD-1 is a secreted protein that forms a complex with radioprotective 105 (RP105) and this complex plays a crucial role in lipopolysaccharide (LPS) recognition by B cells. Disease progression is known to improve in RP105-deficient lupus-prone MRL(lpr/lpr) mice. Furthermore, a soluble form of the homologous MD-2 protein is present in the plasma of septic patients and can opsonize gram-negative bacteria in cooperation with Toll-like receptor (TLR) 4. We have now established a flow cytometry-based assay to detect the soluble form of murine MD-1 (sMD-1) and explored potential roles in autoimmunity. The assay was quantitative and validated with sera from MD-1-deficient mice. Interestingly, heat-inactivated murine serum diminished the ability of sMD-1 to bind RP105. The sMD-1 was secreted by bone marrow-derived macrophages from C57BL/6 mice. Autoimmune prone MRL(lpr/lpr) mice had higher levels of sMD-1 than control MRL(+/+) mice, and levels markedly increased with disease progression. Expression of MD-1 but not MD-2 mRNA increased with age in the liver and kidney of MRL(lpr/lpr) mice. Finally, immunohistochemical analyses revealed that MD-1 was present in infiltrated macrophages within perivascular lesions of the MRL(lpr/lpr) kidney. This correlation suggests that sMD-1 may contribute to pathogenesis in this autoimmune disease model.
authors: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors: Sumiyo
authors: S
authors: Sasaki
authors: Yoshinori
authors: Y
authors: Nagai
authors: Tsutomu
authors: T
authors: Yanagibashi
authors: Yasuharu
authors: Y
authors: Watanabe
authors: Masashi
authors: M
authors: Ikutani
authors: Ai
authors: A
authors: Kariyone
authors: Koichi
authors: K
authors: Tsuneyama
authors: Yoshikatsu
authors: Y
authors: Hirai
authors: Kiyoshi
authors: K
authors: Takatsu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D054730:Protein Interaction Domains and Motifs; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D044967:Serum / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C490500:Ly78 protein, mouse; C113553:Ly86 protein, mouse; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D012333:RNA, Messenger