Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase.

Abstract:

:The functionality of the disintegrin-like/cysteine-rich domains of snake venom metalloproteinases (SVMPs) has been shown to reside in the cysteine-rich region, which can interact with VWA-containing proteins. Recently, the hyper-variable region (HVR) of the cysteine-rich domain was suggested to constitute a potential protein-protein adhesive interface. Here we show that recombinant proteins of HF3, a hemorrhagic P-III SVMP, containing the cysteine-rich domain (disintegrin-like/cysteine-rich and cysteine-rich proteins) but not the disintegrin-like protein were able to significantly increase leukocyte rolling in the microcirculation. Peptides from the HVR also promoted leukocyte rolling and this activity was inhibited by anti-alpha(M)/beta2 antibodies. These results show, for the first time, that the cysteine-rich domain and its HVR play a role in triggering pro-inflammatory effects mediated by integrins.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Menezes MC,Paes Leme AF,Melo RL,Silva CA,Della Casa M,Bruni FM,Lima C,Lopes-Ferreira M,Camargo AC,Fox JW,Serrano SM

doi

10.1016/j.febslet.2008.10.034

subject

Has Abstract

pub_date

2008-11-26 00:00:00

pages

3915-21

issue

28

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(08)00866-1

journal_volume

582

pub_type

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