Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice

Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice. We examined whether the retroviral envelope antigen, gp70, is a major nephritogenic antigen in ddY mice, a murine model of spontaneous mesangial glomerulonephritis associated with IgA and IgG deposition. Immunofluorescence microscopy revealed that the mesangial gp70 deposition increased with age in mice over 24 weeks old, as did the IgG and IgA deposits. Immunoelectron microscopy demonstrated the reaction products of gp70 superimposed on the electron dense deposits in the mesangial matrix. Various amounts of serum gp70 were detected in mice as young as 12 weeks without any apparent increase with age. There was no correlation between the serum level of gp70 and the extent of the glomerular gp70 deposition, whereas mice with heavier IgA deposition had higher mean levels of serum IgA. The absorption test demonstrated that significant amounts of serum gp70 composed immune complexes in 40 week-old ddY mice developing glomerulonephritis; however, this bound form of gp70 was not observed in 12 week-old mice without glomerulonephritis. Systemic examinations by immunofluorescence staining showed that gp70 was mainly localized in various lymphoid tissues. These findings suggest that the gp70 antigen, mostly derived from lymphoid cells, may circulate as immune complexes and accumulate in the mesangial area, thus contributing to the development of glomerulonephritis in these mice. In addition, the pathogenic role of the increased IgA production in these mice was discussed

Comparative histopathological studies in the early stages of acute pathogenic and nonpathogenic SHIV-infected lymphoid organs

AbstractTo clarify the early pathological events in simian and human immunodeficiency chimeric virus (SHIV)-infected lymphoid organs, we examined rhesus macaques infected with an acute pathogenic SHIV (SHIV89.6P) or a nonpathogenic SHIV (NM-3rN) by sequential biopsies and serial necropsies. In the SHIV89.6P-infected monkeys, acute thymic involution as shown by increased cortical tingible-body macrophages and by neutrophilic infiltrates without follicular aggregation in the medulla began within 14 days postinoculation (dpi). Cells that were strongly positive for the virus were identified in the thymic medulla. SHIV89.6P-infected lymph nodes showed severe paracortical lymphadenitis with scattered virus-positive cells at 14 dpi and they developed paracortical depletion without the obvious follicular involution. In contrast, NM-3rN-infected monkeys showed no signs of thymic dysinvolution and the lymph nodes exhibited only follicular hyperplasia. NM-3rN-infected monkeys showed much fewer virus-positive cells in these lymphoid tissues than did SHIV89.6P-infected monkeys during the same period. These differences clearly reflect the difference in the virulence of these SHIVs

蛍光標識微粒子-フローサイトメトリー法による細胞表面IgA結合部位の検索法の開発

本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである京都大学0048新制・課程博士博士(医学)甲第5141号医博第1403号新制||医||540(附属図書館)UT51-92-K331京都大学大学院医学研究科病理系専攻(主査)教授 鈴木 康弘, 教授 内田 温士, 教授 杉山 武敏学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Proinsulin C-peptide activates α-enolase : implications for C-peptide-cell membrane interaction

Proinsulin C-peptide shows beneficial effects on microvascular complications of type 1 diabetes. However, the possible occurrence of membrane C-peptide receptor(s) has not been elucidated. The aim of this study was to identify and characterize membrane proteins to which C-peptide binds. The enzyme α-enolase was co-immunoprecipitated with C-peptide after chemical cross-linking to HL-60 cell surface proteins, and identified by mass spectrometry. Recombinant α-enolase activity was modulated by C-peptide, with a significant decrease in Km for 2-phosphoglycerate without affecting Vmax. The enzyme modulation by C-peptide was abolished when C-terminal basic lysine residue (K434) of the enzyme was replaced by neutral alanine or acidic glutamate, but not with basic arginine. The enzyme modulation by C-peptide was reproduced with the C-peptide fragments containing glutamate corresponding to position 27 (E27) of the full-length C-peptide. Addition of a lysine analogue to the assay and A31 cell culture abrogated the enzyme modulation and MAP kinase activation by C-peptide, respectively. The results indicate that C-peptide has the capacity to activate α-enolase via a specific interaction between E27 of the peptide and K434 of the enzyme. Since α-enolase plays a role as a cell surface receptor for plasminogen, it may conceivably also serve as a receptor for C-peptide in vivo