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Complex regulation of human neutrophil activation by actin filaments: dihydrocytochalasin B and botulinum C2 toxin uncover the existence of multiple cation entry pathways
Author(s) -
WenzelSeifert Katharina,
Lentzen Hans,
Aktories Klaus,
Seifert Roland
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.61.6.703
Subject(s) - exocytosis , thapsigargin , actin , microbiology and biotechnology , biology , superoxide , n formylmethionine leucyl phenylalanine , lectin , biophysics , chemotaxis , biochemistry , secretion , receptor , intracellular , enzyme
Abstract In human neutrophils, the chemotactic peptide, N ‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenalalanine (fMLP), the Ca 2 +‐ATPase inhibitor, thapsigargin, and the lectins, concanavalin A (Con A) and mistletoe lectin I (ML I), stimulate the entry of Ca 2+ and Na + with subsequent activation of exocytosis and superoxide anion (O 2 – ) formation. We studied the role of actin in neutrophil activation. The actin filament‐disrupting substances, dihydrocytochalasin B (dhCB) and botulinum C2 toxin (C2 toxin) potentiated fMLP‐ and lectin‐stimulated Ca 2+ ‐ and Na + entry. Lectin‐induced Mn 2+ entry was enhanced by actin disruption, whereas fMLP‐triggered Mn 2+ entry was unaffected. dhCB and C2 toxin inhibited fMLP‐ and lectin‐stimulated Ba 2+ influx. The actin disrupters also inhibited fMLP‐ and ML I‐induced Sr 2+ influx, whereas Con A‐stimulated Sr 2+ entry was not influenced by dhCB and C2 toxin. Thapsigargin‐stimulated cation entry was not altered by actin disruption. DhCB and botulinum C2 toxin potentiated lysozyme release induced by all four stimuli. Con A and ML I per se activated O 2 – formation only in the presence and not in the absence of dhCB. Con A potentiated the stimulatory effects of ML I on O 2 – formation in the presence of dhCB and primed neutrophils to respond to ML I in the absence of dhCB. Our data indicate the following: (1) dhCB and C2 toxin uncover the existence of multiple cation entry pathways in neutrophils; (2) actin disruption facilitates exocytosis and O 2 – formation by enhancement of Ca 2+ ‐ and Na + entry and by altering the function of proteins involved in activation of secretion and O 2 – formation; and (3) Con A and ML I, which possess different sugar specificities, activate different signaling pathways in neutrophils. J. Leukoc. Biol . 61: 703–711; 1997.