EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha 4 integrin and attenuates lymphocyte infiltration of langerhans islets in pancreas and salivary glands in nonobese diabetic mice
C. Brando et al., EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha 4 integrin and attenuates lymphocyte infiltration of langerhans islets in pancreas and salivary glands in nonobese diabetic mice, BIOC BIOP R, 267(1), 2000, pp. 413-417
Citations number
15
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
The venom of Echis carinatus suchoreki contains a monomeric disintegrin ech
istatin (Mr 5,500 Da) that strongly inhibits alpha IIb beta 3, alpha v beta
3, and alpha 5 beta 1 integrins and a heterodimeric disintegrin called EC3
(M-r 14,762 Da). At nanomolar concentration, EC3 inhibits adhesion of huma
n cell lilies expressing alpha 4 beta 1 and alpha 4 beta 7 to immobilized V
CAM-1; it has a lower inhibitory effect on alpha 5 beta 1-mediated cell adh
esion. In this study, we demonstrated that EC3, in contrast to echistatin,
inhibited binding of monoclonal anti-alpha 4 and anti-alpha 5 antibodies to
cells expressing alpha 4 beta 7. In a dose-dependent manner and to the sam
e extent, EC3 inhibited adhesion of Jurkat cells and murine splenic lymphoc
ytes to immobilized VCAM-1, whereas echistatin was not active. EC3 injected
intraperitoneally into nonobese diabetic (NOD mice) suppressed development
of insulitis and sialoadenitis, whereas echistatin had no significant effe
ct, We propose that the effect of EC3 is mediated, at least, in part, by bl
ocking alpha 4 beta 1 and alpha 4 beta 7 on murine lymphocytes. (C) 2000 Ac
ademic Press.