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

Abstract

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-alpha(M) 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.

• Authors: Carlos A Silva, Juliana P Zuliani, Marina T Assakura, Reinhard Mentele, Antonio C M Camargo, Catarina F P Teixeira, Solange M T Serrano
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 322 Issue 3 Pg. 950-6 (Sep 24 2004) ISSN: 0006-291X [Print] United States
• PMID: 15336556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Macrophage-1 Antigen
• Peptide Fragments
• Recombinant Proteins
• Snake Venoms
• Metalloproteases

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• Bothrops
• Cloning, Molecular
• DNA, Complementary (genetics)
• Macrophage-1 Antigen (drug effects, metabolism)
• Male
• Metalloproteases (isolation & purification, pharmacology)
• Mice
• Molecular Sequence Data
• Peptide Fragments (chemistry, pharmacology)
• Phagocytosis (drug effects)
• Polymerase Chain Reaction
• Recombinant Proteins (pharmacology)
• Snake Venoms (enzymology, pharmacology)