title: Actin assembly and regulation of neutrophil function: effects of cytochalasin B and tetracaine on chemotactic peptide-induced O2- production and degranulation.
abstract: Several studies indicate that the actin filament system is not only involved in cell motility, but also in the regulation of other neutrophil functions. The aim of the present investigation was to examine the mechanisms by which actin filament formation participates in the control of the respiratory burst and degranulation in human neutrophils. The approach taken was to use both an inhibitor (cytochalasin B) and a potentiator (tetracaine) of formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe)-induced actin polymerization. The total inhibition of fMet-Leu-Phe-induced actin polymerization in cytochalasin B-treated cells was accompanied by an impressive potentiation of both oxidase activity and degranulation (azurophilic and specific granules). However, preincubation with tetracaine, which causes an enhanced accumulation of F-actin in the periphery of fMet-Leu-Phe-stimulated cells, also augmented the rate and duration of peptide-induced superoxide anion production, but inhibited degranulation (specific granules). A likely explanation for the potentiating effects of cytochalasin B and tetracaine is provided by our observation that both of these substances reduced the acid-resistant binding of fMet-Leu-Phe (interpreted as a decrease in the internalization of fMet-Leu-Phe-receptor-complexes), resulting in an enhanced formation of second messengers (diacylglycerol). The findings that tetracaine potentiated the activity of the oxidase, whereas it inhibited degranulation (specific granules), suggest that actin polymerization per se plays a role in the latter process. Consequently, this study argues against the idea of a direct inhibitory effect of F-actin on chemotactic factor-induced oxidase activation, but supports an active role of actin filaments in the translocation and release of granule components.
authors.affiliation: Department of Medical Microbiology, University of Linköping, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Bengtsson
authors.forename: C
authors.initials: C
authors.lastname: Dahlgren
authors.forename: O
authors.initials: O
authors.lastname: Stendahl
authors.forename: T
authors.initials: T
authors.lastname: Andersson
mesh_terms: D000199:Actins / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003571:Cytochalasin B / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013748:Tetracaine / Q000494:pharmacology; D014155:Transcobalamins / Q000378:metabolism
chemical_list: D000199:Actins; D004075:Diglycerides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D014155:Transcobalamins; D013748:Tetracaine; D013481:Superoxides; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D005966:Glucuronidase