PMID- 9201261 OWN - NLM STAT- MEDLINE DCOM- 19970721 LR - 20190516 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 61 IP - 6 DP - 1997 Jun TI - Complex regulation of human neutrophil activation by actin filaments: dihydrocytochalasin B and botulinum C2 toxin uncover the existence of multiple cation entry pathways. PG - 703-11 AB - 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 Ca2+ and Na+ with subsequent activation of exocytosis and superoxide anion (O2-) 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 Mn2+ entry was enhanced by actin disruption, whereas fMLP-triggered Mn2+ entry was unaffected. dhCB and C2 toxin inhibited fMLP- and lectin-stimulated Ba2+ influx. The actin disrupters also inhibited fMLP- and ML I-induced Sr2+ influx, whereas Con A-stimulated Sr2+ 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 O2- formation only in the presence and not in the absence of dhCB. Con A potentiated the stimulatory effects of ML I on O2- 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 O2- formation by enhancement of Ca(2+)- and Na+ entry and by altering the function of proteins involved in activation of secretion and O2- formation; and (3) Con A and ML I, which possess different sugar specificities, activate different signaling pathways in neutrophils. FAU - Wenzel-Seifert, K AU - Wenzel-Seifert K AD - Institut fur Pharmakologie, Freie Universitat Berlin, Germany. FAU - Lentzen, H AU - Lentzen H FAU - Aktories, K AU - Aktories K FAU - Seifert, R AU - Seifert R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Actins) RN - 0 (Cations) RN - 0 (Lectins) RN - 0 (Plant Preparations) RN - 0 (Plant Proteins) RN - 0 (Ribosome Inactivating Proteins, Type 2) RN - 0 (Toxins, Biological) RN - 0 (mistletoe lectin I) RN - 0 (ribosome inactivating protein, Viscum) RN - 11062-77-4 (Superoxides) RN - 24GP945V5T (Barium) RN - 39156-67-7 (dihydrocytochalasin B) RN - 3CHI920QS7 (Cytochalasin B) RN - 42Z2K6ZL8P (Manganese) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 67526-95-8 (Thapsigargin) RN - 9NEZ333N27 (Sodium) RN - EC 3.2.1.17 (Muramidase) RN - EC 3.4.24.69 (Botulinum Toxins) RN - FPM7829VMX (botulinum toxin type C) RN - SY7Q814VUP (Calcium) RN - YZS2RPE8LE (Strontium) SB - IM MH - Actins/blood/drug effects/*physiology MH - Barium/blood MH - Botulinum Toxins/*pharmacology MH - Calcium/blood MH - Cations/*blood MH - Cytochalasin B/*analogs & derivatives/pharmacology MH - Female MH - Humans MH - Ion Transport/drug effects MH - Lectins/pharmacology MH - Male MH - Manganese/blood MH - Muramidase/blood MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophil Activation/*drug effects MH - Neutrophils/drug effects/*metabolism MH - *Plant Preparations MH - *Plant Proteins MH - Ribosome Inactivating Proteins, Type 2 MH - Sodium/blood MH - Strontium/blood MH - Superoxides/blood MH - Thapsigargin/pharmacology MH - Toxins, Biological/pharmacology EDAT- 1997/06/01 00:00 MHDA- 1997/06/01 00:01 CRDT- 1997/06/01 00:00 PHST- 1997/06/01 00:00 [pubmed] PHST- 1997/06/01 00:01 [medline] PHST- 1997/06/01 00:00 [entrez] AID - 10.1002/jlb.61.6.703 [doi] PST - ppublish SO - J Leukoc Biol. 1997 Jun;61(6):703-11. doi: 10.1002/jlb.61.6.703.