Suramin inhibits antibody binding to cell surface antigens and disrupts complement-mediated mesangial cell lysis.
Suramin inhibits immune responses and protects cells against inflammatory cell injury. However, little is known about its mechanisms. Using an in vitro model of glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we investigated the potential protective effects and mechanisms of suramin on immunologic cell injury. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused complement-dependent cell lysis, which was blocked by suramin and its structural analogue NF023 and NF049, but not by PPADS, an antagonist of purinergic receptors. Addition of exogenous ATP also failed to affect MC lysis. Further analysis revealed that suramin interfered with antibody binding to cell membrane antigens and suppressed antibody-induced phosphorylation of several proteins, including p38. Inhibition of p38 with chemical inhibitor significantly attenuated cell injury. Collectively, our results indicate that suramin protects cells against antibody-initiated and complement-dependent cell injury through inhibition of antibody binding to cell surface antigens and suppression of p38 activation. Our study thus provides novel mechanistic insights into the actions of suramin and suggests that suramin might be used to treat certain immune diseases.
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan; Department of Rehabilitation, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Honglan
H
Piao
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Yuan
Y
Chi
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Xiling
X
Zhang
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Zhen
Z
Zhang
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Kun
K
Gao
Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Manabu
M
Niimi
Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Manabu
M
Kamiyama
Department of Rehabilitation, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Jinming
J
Zhang
Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Masayuki
M
Takeda
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan. Electronic address: yao@yamanashi.ac.jp.
Jian
J
Yao
D000818:Animals; D000937:Antigen-Antibody Reactions / Q000187:drug effects / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology / Q000494:pharmacology*; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology / Q000494:pharmacology*; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011817:Rabbits; D051381:Rats; D013498:Suramin / Q000494:pharmacology*
D000954:Antigens, Surface; D007136:Immunoglobulins; D007518:Isoantibodies; C035678:anti-Thy antibody; D013498:Suramin; D003165:Complement System Proteins
Antibody; Cell lysis; Complement; Mesangial cells; Suramin; p38