Concanavalin A and mistletoe lectin I differentially activate cation entry and exocytosis in human neutrophils: lectins may activate multiple subtypes of cation channels.
The mannose-specific lectin, concanavalin A (ConA), activates Ca2+ entry in human neutrophils by an as yet poorly defined mechanism. The question of whether the sugar specificity of lectins influences signal transduction is unresolved too. Therefore, we studied the effects of ConA in comparison to those of the beta-galactoside-specific lectin, mistletoe lectin I (MLI), on cation entry and exocytosis in human neutrophils. ConA- and MLI-activated influx of Ca2+, Mn2+, Ba2+, Sr2+, and Na+. Lectin-induced cation influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxy-phenethyl) -1H-imidazole hydrochloride (SK&F 96365) and Gd3+. There were differences in the effectiveness of lectins to activate cation entry and of SK&F 96365, Gd3+, and modulators of protein phosphorylation to block entry. MLI but not ConA inhibited thapsigargin-induced Ca2+ entry. Under whole-cell voltage-clamp conditions, MLI activated an inward current that was substantially reduced by removal of extracellular Na+. ConA and MLI synergistically activated Ca2+ entry and lysozyme release. SK&F 96365 and removal of extracellular Ca2+ and Na+ partially inhibited exocytosis. Our data show the following: (1) ConA and MLI activate monovalent and divalent cation entry in human neutrophils by a SK&F 96365- and Gd3+-sensitive pathway, presumably nonselective cation channels. (2) Ca2+ and Na+ entry are involved in the activation of exocytosis by lectins. (3) The differential and/or synergistic effects of ConA and MLI on cation entry and exocytosis may be attributable to mannose- and beta-galactoside-specific activation of signal transduction pathways, i.e., activation of multiple and differentially regulated subtypes of nonselective cation channels.
Wenzel-Seifert
K
K
Institut für Pharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Krautwurst
D
D
Lentzen
H
H
Seifert
R
R
D001464:Barium / Q000097:blood / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood / Q000493:pharmacokinetics; D002413:Cations, Divalent / Q000493:pharmacokinetics; D003208:Concanavalin A / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects*; D005260:Female; D005453:Fluorescence; D006801:Humans; D007473:Ion Channels / Q000145:classification / Q000187:drug effects*; D008297:Male; D008670:Metals / Q000097:blood / Q000493:pharmacokinetics*; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000097:blood / Q000493:pharmacokinetics; D013268:Stimulation, Chemical; D013324:Strontium / Q000097:blood / Q000493:pharmacokinetics; D019284:Thapsigargin / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology*
D002413:Cations, Divalent; D007473:Ion Channels; D008670:Metals; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D003208:Concanavalin A; D001464:Barium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019284:Thapsigargin; D012964:Sodium; D009113:Muramidase; D002118:Calcium; D013324:Strontium