Ginkgolide B stimulates signaling events in neutrophils and primes defense activities.
Ginkgolide B (GKB) is a bioactive component of the standardized extract from the leaves of the Ginkgo biloba tree (EGb 761), which is used in Chinese and in occidental medicine. GKB is known as a platelet-activating factor receptor antagonist. Here, we provide evidence that GKB per se (0.25-5 microM) stimulated tyrosine phosphorylation of proteins, phospholipase D activation, calcium transients, and activation of p38 but not p44/42 Map kinases in human polymorphonuclear leukocytes (PMN). These stimulatory effects remained relatively weak and primed PMN for subsequent stimulation of respiratory burst (RB) or directed locomotion by the chemoattractant fMet-Leu-Phe (fMLP) or complement-derived factor C5a. A similar RB priming was observed with rat exudate PMN after in vivo administration of EGb 761 (25 and 50 mg/kg) to rats before pleurisy induction. Thus, GKB primarily induces activation of intracellular signaling events and has the potential to prime cellular functions such as PMN defense activities.
Lenoir
Monique
M
Institut Cochin, Département de Biologie Cellulaire, INSERM U567, CNRS UMR 8104, 27 rue du Faubourg St. Jacques, Bat G. Roussy, 75679 Paris Cedex 14, France.
Muntaner
Olivier
O
Pedruzzi
Eric
E
Roch-Arveiller
Monique
M
Tissot
Michèle
M
Drieu
Katy
K
Périanin
Axel
A
D000818:Animals; D002478:Cells, Cultured; D004224:Diterpenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010998:Pleurisy / Q000276:immunology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; C045856:ginkgolide B