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

Milene C Menezes, Adriana F Paes Leme, Robson L Melo, Carlos A Silva, Maisa Della Casa, Fernanda M Bruni, Carla Lima, Mônica Lopes-Ferreira, Antonio C M Camargo, Jay W Fox, Solange M T Serrano

Laboratório Especial de Toxinologia Aplicada-CAT/CEPID, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, Brazil.

FEBS letters 2008 Nov 26

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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.

Citation

Milene C Menezes, Adriana F Paes Leme, Robson L Melo, Carlos A Silva, Maisa Della Casa, Fernanda M Bruni, Carla Lima, Mônica Lopes-Ferreira, Antonio C M Camargo, Jay W Fox, Solange M T Serrano. Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase. FEBS letters. 2008 Nov 26;582(28):3915-21