Activation of cellular functions in macrophages by venom secretory Asp-49 and Lys-49 phospholipases A(2).
The in vitro effects of myotoxin III (MT-III), an Asp-49 catalytically-active phospholipase A(2), and myotoxin II (MT-II), a catalytically-inactive Lys-49 variant, isolated from Bothrops asper snake venom, on phagocytosis and production of hydrogen peroxide (H(2)O(2)) by thioglycollate-elicited macrophages were investigated. MT-II and MT-III were cytotoxic to mouse peritoneal macrophages at concentrations higher than 25 microg/ml. At non-cytotoxic concentrations, MT-II stimulated Fcgamma, complement, mannose and beta-glucan receptors-mediated phagocytosis, whereas MT-III stimulated only the mannose and beta-glucan receptors-mediated phagocytosis. Moreover, both myotoxins induced the release of H(2)O(2) by thioglycollate-elicited macrophages, MT-III being the most potent stimulator. MT-II induced the release of H(2)O(2) only at a concentration of 3.2 microg/ml (130% increment) while MT-III induced this effect at all concentrations tested (0.5-2.5 microg/ml; average of 206% increment). It is concluded that, at non-cytotoxic concentrations, MT-II and MT-III activate defense mechanisms in macrophages up regulating phagocytosis, mainly via mannose and beta-glucan receptors, and the respiratory burst.
Zuliani
Juliana Pavan
JP
Laboratorio de Farmacologia, Instituto Butantan, Av.Vital Brazil, 1500-CEP 05503-900 Sao Paulo, SP, Brazil. cteixer@usp.br
Gutiérrez
José María
JM
Casais e Silva
Luciana Lyra
LL
Coccuzzo Sampaio
Sandra
S
Lomonte
Bruno
B
Pereira Teixeira
Catarina de Fátima
Cde F
D000818:Animals; D017837:Bothrops / Q000378:metabolism*; D002176:Candida albicans; D003165:Complement System Proteins / Q000502:physiology; D003435:Crotalid Venoms / Q000201:enzymology* / Q000494:pharmacology*; D054501:Group II Phospholipases A2; D006861:Hydrogen Peroxide / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000502:physiology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D010741:Phospholipases A / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000502:physiology; D030162:Reptilian Proteins; D012756:Sheep; D015054:Zymosan
D003435:Crotalid Venoms; D007141:Immunoglobulin Fc Fragments; D007202:Indicators and Reagents; D011971:Receptors, Immunologic; D030162:Reptilian Proteins; C045268:beta-glucan receptor; D003165:Complement System Proteins; D015054:Zymosan; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C061056:myotoxin II, Bothrops asper; D008358:Mannose