Parabutoporin--an antibiotic peptide from scorpion venom--can both induce activation and inhibition of granulocyte cell functions.
Parabutoporin (PP) affects motility and NADPH oxidase activity in normal human polymorphonuclear neutrophils and in granulocytic HL-60 cells. These PP-induced interactions utilize a Rac activation pathway. PP induces chemotaxis of neutrophils and HL-60 cells via a pertussis toxin-sensitive way, thus using trimeric G-proteins. The enhanced chemotaxis is also apparent in undifferentiated HL-60 cells which lack functional formyl peptide receptors. On the other hand, PP strongly reduces the superoxide production by the NADPH oxidase complex after either PMA or fMLP activation of granulocytes. These combined results strongly suggest a direct activation of G-proteins and subsequent Rac activation as the basis for the observed effects. The unexpected inhibitory effect of PP, despite Rac activation, on superoxide production in granulocytes is explained by the direct interaction of membrane localized PP which prevents the formation of a functional NADPH oxidase complex.
Willems
Jean
J
Interdisciplinary Research Center, KULAK, University Campus, B-8500 Kortrijk, Belgium. jean.willems@kulak.ac.be
Moerman
Leentje
L
Bosteels
Suzanne
S
Bruyneel
Erik
E
Ryniers
Filip
F
Verdonck
Fons
F
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002457:Cell Extracts; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002457:Cell Extracts; D012604:Scorpion Venoms; C496148:parabutoporin, Parabuthus schlechteri; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D020744:rac GTP-Binding Proteins