title: 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.
authors.affiliation: Laboratório Especial de Toxinologia Aplicada-CAT/CEPID, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, Brazil.
authors.forename: Milene C
authors.initials: MC
authors.lastname: Menezes
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Paes Leme
authors.forename: Robson L
authors.initials: RL
authors.lastname: Melo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Silva
authors.forename: Maisa
authors.initials: M
authors.lastname: Della Casa
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Bruni
authors.forename: Carla
authors.initials: C
authors.lastname: Lima
authors.forename: Mônica
authors.initials: M
authors.lastname: Lopes-Ferreira
authors.forename: Antonio C M
authors.initials: AC
authors.lastname: Camargo
authors.forename: Jay W
authors.initials: JW
authors.lastname: Fox
authors.forename: Solange M T
authors.initials: SM
authors.lastname: Serrano
mesh_terms: 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
chemical_list: D003435:Crotalid Venoms; D010455:Peptides; D008666:Metalloendopeptidases; C069317:hemorrhagic metalloproteinase; D003545:Cysteine