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+ ent ry in human neutrophils by an as yet poorly defined mechanism. The que stion of whether the sugar specificity of lectins influences signal tr ansduction is unresolved too. Therefore, we studied the effects of Con A in comparison to those of the beta-galactoside-specific lectin, mist letoe lectin I (MLI), on cation entry and exocytosis in human neutroph ils. ConA- and MLI-activated influx of Ca2+, Mn2+, Ba2+, Sr2+, and Na. Lectin-induced cation influxes were inhibited by -[3-(4-methoxypheny l)propoxy]-4-methoxy-phenethyl} -1H-imidazole hydrochloride (SK&F 9636 5) and Gd3+. There were differences in the effectiveness of lectins to activate cation entry and of SK&F 96365, Gd3+, and modulators of prot ein phosphorylation to block entry. MLI but not ConA inhibited thapsig argin-induced Ca2+ entry. Under whole-cell voltage-clamp conditions, M LI activated an inward current that was substantially reduced by remov al of extracellular Na+. ConA and MLI synergistically activated Ca2+ e ntry 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 hum an 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 s ynergistic effects of ConA and MLI on cation entry and exocytosis may be attributable to mannose- and beta-galactoside-specific activation o f signal transduction pathways, i.e., activation of multiple and diffe rentially regulated subtypes of nonselective cation channels.