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BIBTEX RIS

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

2008; Wiley; Volume: 582; Issue: 28 Linguagem: Inglês

10.1016/j.febslet.2008.10.034

1873-3468

Milene C. Menezes, Adriana Franco Paes Leme, Robson L. Melo, Carlos Alberto-Silva, Maisa Della Casa, Fernanda Miriane Bruni, Carla Lima, Mônica Lopes‐Ferreira, Antônio Carlos Martins de Camargo, Jay W. Fox, Solange M.T. Serrano,

Blood Coagulation and Thrombosis Mechanisms

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 /beta 2 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.