Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase.
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.
Menezes
Milene C
MC
Laboratório Especial de Toxinologia Aplicada-CAT/CEPID, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, Brazil.
Paes Leme
Adriana F
AF
Melo
Robson L
RL
Silva
Carlos A
CA
Della Casa
Maisa
M
Bruni
Fernanda M
FM
Lima
Carla
C
Lopes-Ferreira
Mônica
M
Camargo
Antonio C M
AC
Fox
Jay W
JW
Serrano
Solange M T
SM
D000595:Amino Acid Sequence; D000818:Animals; D017837:Bothrops; D002384:Catalysis; D003435:Crotalid Venoms / Q000201:enzymology*; D003545:Cysteine / Q000737:chemistry; D036904:Leukocyte Rolling / Q000187:drug effects*; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000235:genetics
D003435:Crotalid Venoms; D010455:Peptides; D008666:Metalloendopeptidases; C069317:hemorrhagic metalloproteinase; D003545:Cysteine