In vitro cytotoxicity of IgG antibodies on vascular endothelial cells from patients with endemic peripheral vascular disease in Taiwan.
A unique peripheral vascular disorder called 'blackfoot disease' is endemic in a limited area on the south-west coast of Taiwan. Clinically, the signs and symptoms of blackfoot disease (BFD) are similar to those of arteriosclerosis and Buerger's disease. A destruction of vascular endothelial cells (ECs) takes place at an early stage in the affected limbs. Currently, the cause of BFD is believed to be artesian drinking water containing a high concentration of arsenic and/or humic substances, although the mechanism of EC destruction is not entirely understood. The purpose of the present study was to examine the factors related to EC damage in BFD. Thus, we investigated the effects of purified IgG collected from patients with BFD (BFD-IgG) and from normal controls (N-IgG) on cultured EC. We found that: (1) EC binding activity of BFD-IgG was significantly higher than that of N-IgG; (2) BFD-IgG, at a concentration higher than 100 microg/ml but not N-IgG, induced concentration-dependent EC cytotoxicity; (3) BFD-IgG at a concentration of 100 microg/ml stimulated neither the release of von Willebrand factor nor the expression of intercellular adhesion molecule-1 by EC. Fluorescent video microscopic examination revealed an increase in transcapillary and interstitial diffusion of nailfold capillary loops in clinically normal fingers of BFD patients. These findings strongly suggested that immunological mechanisms played a significant role in the pathogenesis of BFD. We propose that only persons who produce the IgG anti-endothelial cell antibody are potential victims of BFD.
Yu
H S
HS
Department of Dermatology, Kaohsiung Medical College, Taiwan. dermyu@cc.kmc.edu.tw
Chang
K L
KL
Kao
Y H
YH
Yu
C L
CL
Chen
G S
GS
Chang
C H
CH
Fang
K T
KT
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D002196:Capillaries / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D019353:Endemic Diseases; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D008297:Male; D016491:Peripheral Vascular Diseases / Q000453:epidemiology* / Q000276:immunology*; D011485:Protein Binding; D013624:Taiwan / Q000453:epidemiology; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1