Activation of α Mβ 2-mediated phagocytosis by HF3, a P-III class metalloproteinase isolated from the venom of Bothrops jararaca

• Published in: Biochemical and biophysical research communications Vol. 322; no. 3; pp. 950 - 956
• Main Authors: Silva, Carlos A., Zuliani, Juliana P., Assakura, Marina T., Mentele, Reinhard, Camargo, Antonio C.M., Teixeira, Catarina F.P., Serrano, Solange M.T.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 24-09-2004
• Subjects: Disintegrin-like/cysteine-rich domains; Inflammation; Integrin α Mβ 2; Macrophage; Phagocytosis; Platelet aggregation; Snake venom metalloproteinase; Disintegrin-like/cysteine-rich domains; Snake venom metalloproteinase; Platelet aggregation; Inflammation; Integrin α Mβ 2; Phagocytosis; Macrophage
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.08.012

The integrin α
Mβ
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 α
Mβ
2-mediated phagocytosis of opsonized-zymosan particles by macrophages. HF3 and DC-HF3 significantly increased phagocytosis and this activity was inhibited by anti-α
M and anti-β
2 antibodies. The data show the ability of P-III metalloproteinases to activate macrophages for phagocytosis through integrin α
Mβ
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 α
Mβ
2 integrin by a metalloproteinase containing disintegrin-like/cysteine-rich domains.