MP17-04 COMPLEMENT ACTIVATION MECHANISM ACTIVATED BY AUTOANTIGEN RECOGNITION DURING GROWTH OF BENIGN PROSTATIC HYPERPLASIA

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2017MP17-04 COMPLEMENT ACTIVATION MECHANISM ACTIVATED BY AUTOANTIGEN RECOGNITION DURING GROWTH OF BENIGN PROSTATIC HYPERPLASIA Junya Hata, Kanako Matsuoka, Yuichi Sato, Hidenori Akaihata, Masao Kataoka, Soichiro Ogawa, Nobuhiro Haga, Kei Ishibashi, Ken Aikawa, and Yoshiyuki Kojima Junya HataJunya Hata More articles by this author , Kanako MatsuokaKanako Matsuoka More articles by this author , Yuichi SatoYuichi Sato More articles by this author , Hidenori AkaihataHidenori Akaihata More articles by this author , Masao KataokaMasao Kataoka More articles by this author , Soichiro OgawaSoichiro Ogawa More articles by this author , Nobuhiro HagaNobuhiro Haga More articles by this author , Kei IshibashiKei Ishibashi More articles by this author , Ken AikawaKen Aikawa More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.593AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The association between the pathogenesis of benign prostatic hyperplasia (BPH) and inflammation has recently received attention. We previously showed that not only the inflammation response pathway, but also the classical complement pathway is activated in BPH tissue from model rats with stroma-dominant BPH. The classical complement pathway is activated by autoantigens that recognize immune complexes and it is responsible for various diseases via a mechanism that amplifies inflammation. We postulated that immune complexes amplify inflammation through complement activation, which leads to prostatic proliferation. Therefore, we expressed complement factors, analyzed their functions, and identified autoantigens to understand the pathogenic mechanism of BPH. METHODS Fetal urogenital sinus (UGS) isolated from male 20-day-old rat embryos was implanted into the ventral prostate of pubertal male rats to create rat models of BPH. Complement factors were expressed and functionally analyzed in BPH tissues, and then serum concentrations of IgG and the expression of complement factors in BPH tissues were assessed. We immunoprecipitated BPH protein using an anti-IgG antibody to identify antigens, and analyzed the protein by mass spectrometry after SDS-PAGE separation. The expression of complement factors in human BPH tissue was also analyzed. RESULTS The expression of complement factors C1q, C3, MBL, factor B, and MAC was significantly up-regulated in tissues from BPH rats compared with those from normal rats (p<0.01). The classical complement pathway was initially activated, followed by an alternative complement pathway activated in BPH. These complement factors were also up-regulated mostly in stromal areas of human BPH. The serum IgG concentration was significantly increased (398.1 ng/mL, p<0.01) in rat BPH and IgG was deposited in stromal areas of the BPH. Mass spectrometry of IgG binding protein identified annexin, Hsp90, and β-actin as antigens of immunocomplexes. CONCLUSIONS We clarified that the immune system is responsible for the development of BPH. Complement pathway activation by immunocomplexes recognizing annexin, Hsp90, and β-actin as autoantigens might be responsible for the pathogenesis of BPH. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e213 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Junya Hata More articles by this author Kanako Matsuoka More articles by this author Yuichi Sato More articles by this author Hidenori Akaihata More articles by this author Masao Kataoka More articles by this author Soichiro Ogawa More articles by this author Nobuhiro Haga More articles by this author Kei Ishibashi More articles by this author Ken Aikawa More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...