Complex regulation of human neutrophil activation by actin filaments: dihydrocytochalasin B and botulinum C2 toxin uncover the existence of multiple cation entry pathways

Journal/Book: J-Leukoc-Biol 61 (6), 703-711. 1997;

Abstract: In human neutrophils, the chemotactic peptide,N-formyl-L-methionyl-L-leucyl-L-phenalalanine (fMLP), the Ca(2+)-ATPaseinhibitor, thapsigargin, and the lectins, concanavalin A (Con A) andmistletoe lectin I (ML I), stimulate the entry of Ca2+ and Na+ withsubsequent activation of exocytosis and superoxide anion (O2-)formation. We studied the role of actin in neutrophil activation. Theactin filament-disrupting substances, dihydrocytochalasin B (dhCB) andbotulinum C2 toxin (C2 toxin) potentiated fMLP- and lectin-stimulatedCa(2+)- and Na+ entry. Lectin-induced Mn2+ entry was enhanced by actindisruption, whereas fMLP-triggered Mn2+ entry was unaffected. dhCB andC2 toxin inhibited fMLP- and lectin-stimulated Ba2+ influx. The actindisrupters also inhibited fMLP- and ML I-induced Sr2+ influx, whereasCon A-stimulated Sr2+ entry was not influenced by dhCB and C2 toxin.Thapsigargin-stimulated cation entry was not altered by actindisruption. DhCB and botulinum C2 toxin potentiated lysozyme releaseinduced by all four stimuli. Con A and ML I per se activated O2-formation only in the presence and not in the absence of dhCB. Con Apotentiated the stimulatory effects of ML I on O2- formation in thepresence of dhCB and primed neutrophils to respond to ML I in theabsence of dhCB. Our data indicate the following: (1) dhCB and C2 toxinuncover the existence of multiple cation entry pathways in neutrophils;(2) actin disruption facilitates exocytosis and O2- formation byenhancement of Ca(2+)- and Na+ entry and by altering the function ofproteins involved in activation of secretion and O2- formation; and (3)Con A and ML I, which possess different sugar specificities, activatedifferent signaling pathways in neutrophils. Author.

Keyword(s): ACTINS/BL (blood), DE (drug effects), PH (physiology)

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