Activation of alpha(M)beta(2)-mediated phagocytosis by HF3, a P-III class metalloproteinase isolated from the venom of Bothrops jararaca

Autor(es)

Silva, Carlos A. ; Zuliani, Juliana P. ^[2] ; Assakura, Marina T. ; Mentele, Reinhard ; Camargo, Antonio C. M. ; Teixeira, Catarina F. P. ; Serrano, Solange M. T.

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 322, n. 3, p. 950-956, Sept. 2004.
• Área do conhecimento: Ciências Biológicas - Farmacologia
• Assunto(s): Farmacologia Venenos de origem animal Bothrops jararaca Proteínas Metaloproteinases

Resumo

The integrin alpha(M)beta(2) regulates important cell functions in inflammation being the primary phagocytic receptor on macrophages. HF3, a metalloproteinase isolated from Bothrops jararaca venom, is a potent hemorrhagic toxin. A cDNA encoding HF3 indicated that it is a multidomain molecule composed of a pro-domain, a catalytic domain with a zinc binding sequence, followed by disintegrin-like and cysteine-rich domains. It is known that metalloproteinases play a relevant role in the pathogenesis of venom-induced local tissue damage including inflammation. In this study we evaluated the effects of native HF3 and its recombinant disintegrin-like/ cysteine-rich domains (DC-HF3) on alpha(M)beta(2)-mediated phagocytosis of opsonized-zymosan particles by macrophages. HF3 and DC- HF3 significantly increased phagocytosis and this activity was inhibited by anti-(alphaM) and anti-beta(2) antibodies. The data show the ability of P-III metalloproteinases to activate macrophages for phagocytosis through integrin alpha(M)beta(2) and suggest that the disintegrin-like/ cysteine-rich domains are important for this effect. This is the first report on the activation of phagocytosis via alpha(M)beta(2) integrin by a metalloproteinase containing disintegrin-like/cysteine-rich domains. (AU)

• Processo FAPESP: 02/13863-2 - Efeitos dos venenos de Bothrops asper e de Crotalus durissus terrificus, das miotoxinas MT-II e MT-III, crotoxina e crotapotina sobre a liberação de prostanóides e a expressão de ciclooxigenases: estudos in vivo e in vitro
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/01009-7 - Estudos da sinalização intracelular e proteínas de citoesqueleto no processo de fagocitose por macrófagos induzido por duas toxinas com estrutura de Fosfolipase A2 (mt-ii e MT-III), isoladas no veneno de Bothrops asper
• Beneficiário: Juliana Pavan Zuliani
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 98/14307-9 - Center for Applied Toxinology
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs