On the mechanism of oscillations in neutrophils.
We have investigated the regulation of the oscillatory generation of H(2)O(2) and oscillations in shape and size in neutrophils in suspension. The oscillations are independent of cell density and hence do not represent a collective phenomena. Furthermore, the oscillations are independent of the external glucose concentration and the oscillations in H(2)O(2) production are 180 degrees out of phase with the oscillations in NAD(P)H. Cytochalasin B blocked the oscillations in shape and size whereas it increased the period of the oscillations in H(2)O(2) production. 1- and 2-butanol also blocked the oscillations in shape and size, but only 1-butanol inhibited the oscillations in H(2)O(2) production. We conjecture that the oscillations are likely to be due to feedback regulations in the signal transduction cascade involving phosphoinositide 3-kinases (PI3K). We have tested this using a simple mathematical model, which explains most of our experimental observations.
Brasen
Jens Christian
JC
CelCom, Institute of Biochemistry and Molecular Biology, University of Southern Denmark, Denmark. christianb@bmb.sdu.dk
Barington
Torben
T
Olsen
Lars Folke
LF
D020001:1-Butanol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D003571:Cytochalasin B / Q000494:pharmacology; D025461:Feedback, Physiological; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors; D055503:Protein Multimerization / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D003571:Cytochalasin B; D009249:NADP; D020001:1-Butanol; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010739:Phospholipase D; D002118:Calcium