Activation of superoxide production and differential exocytosis in polymorphonuclear leukocytes by cytochalasins A, B, C, D and E. Effects of various ions.
All of the common cytochalasins activate superoxide anion release and exocytosis of beta-N-acetylglucosaminidase and lysozyme from guinea-pig polymorphonuclear leukocytes (neutrophils) incubated in a buffered sucrose medium. Half-maximal activation of both processes is produced by approx. 0.2 microM cytochalasin A, C greater than 2 microM cytochalasin B greater than or equal to 4-5 microM cytochalasin D, E. While maximal rates of O2- release and extents of exocytosis require extracellular calcium (1-2 mM), replacing sucrose with monovalent cation chlorides is inhibitory to neutrophil activation by cytochalasins. Na+, K+ or choline inhibit either cytochalasin B- or E-stimulated O2- production with IC50 values of 5-10 mM and inhibition occurs whether Cl-, NO3- or SCN- is the anion added with Na+ or K+. Release of beta-N-acetylglucosaminidase in control or cytochalasin B-stimulated cells is inhibited by NaCl(IC50 approximately 10 mM), while cytochalasin E-stimulated exocytosis is reduced less and K+ or choline chloride are ineffective in inhibiting either cytochalasin B- or E-stimulated exocytosis. Release of beta-glucuronidase, myeloperoxidase or acid phosphatase from neutrophils incubated in buffered sucrose is not stimulated by cytochalasin B. Stimulation of either O2- or beta-N-acetylglucosaminidase release by low concentrations of cytochalasin A is followed by inhibition of each at higher concentrations. It appears that all cytochalasins can activate both NAD(P)H oxidase and selective degranulation of neutrophils incubated in salt-restricted media and that differential inhibition of these two processes by monovalent cations and/or anions is produced at some step(s) subsequent to cytochalasin interaction with the cell.
D000818:Animals; D000838:Anions; D002414:Cations, Monovalent; D003572:Cytochalasins / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects*; D006168:Guinea Pigs; D006867:Hydrolases / Q000097:blood; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood*; D013481:Superoxides / Q000097:blood*
D000838:Anions; D002414:Cations, Monovalent; D003572:Cytochalasins; D013481:Superoxides; D006867:Hydrolases; D010100:Oxygen