Anti-endothelial cell IgG from patients with chronic arsenic poisoning induces endothelial proliferation and VEGF-dependent angiogenesis.
An endemic peripheral vascular disorder due to chronic arsenic poisoning, named Blackfoot disease (BFD), occurs in Taiwan. BFD causes destruction of vascular endothelial cells, and an anti-endothelial cell IgG antibody was found in the sera of BFD patients. We studied the role of this IgG antibody (BFD-IgG) in modulating proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) and found that a low concentration of BFD-IgG (200 microg/mL) stimulated endothelial cell growth and increased expressions of vascular cell adhesion molecule-1 (VCAM-1), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF). The apoptosis events appeared not altered by addition of BFD-IgG. An in vitro neoangiogenesis assay demonstrated that BFD-IgG promoted the formation of tube-like structures, which was completely abrogated by anti-VEGF neutralizing antibody and partially by NOS inhibitor, L-NAME. We conclude that BFD-IgG at 200 microg/mL results in cell proliferation and enhanced VEGF-dependent angiogenesis in vitro. Those results suggested that a low concentration of BFD-IgG plays a protective role in the pathogenesis or the progression of BFD.
Hong
Chien-Hui
CH
Department of Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lee
Chih-Hung
CH
Chang
Louis W
LW
Chiou
Min-Hsi
MH
Hsieh
Ming-Chu
MC
Kao
Ying-Hsien
YH
Yu
Hsin-Su
HS
D020261:Arsenic Poisoning / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009389:Neovascularization, Pathologic; D020932:Nerve Growth Factor / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D013624:Taiwan; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D007074:Immunoglobulin G; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D020932:Nerve Growth Factor