Activation of alpha(M)beta(2)-mediated phagocytosis by HF3, a P-III class metalloproteinase isolated from the venom of Bothrops jararaca.
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.
Silva
Carlos A
CA
Laboratorio Especial de Toxinologia Aplicada-CAT/CEPID, Instituto Butantan, CEP 05503-900, Sao Paulo, Brazil.
Zuliani
Juliana P
JP
Assakura
Marina T
MT
Mentele
Reinhard
R
Camargo
Antonio C M
AC
Teixeira
Catarina F P
CF
Serrano
Solange M T
SM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017837:Bothrops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D045726:Metalloproteases / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D012910:Snake Venoms / Q000201:enzymology / Q000494:pharmacology*
D018076:DNA, Complementary; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012910:Snake Venoms; D045726:Metalloproteases