Olsen2003_neutrophil_oscillatory_metabolism

Olsen2003_neutrophil_oscillatory_metabolism

This model is described in the article:

A model of the oscillatory
metabolism of activated neutrophils.

Olsen LF, Kummer U, Kindzelskii AL,
Petty HR.
Biophys. J. 2003 Jan; 84(1):
69-81
Abstract:

We present a two-compartment model to explain the
oscillatory behavior observed experimentally in activated
neutrophils. Our model is based mainly on the
peroxidase-oxidase reaction catalyzed by myeloperoxidase with
melatonin as a cofactor and NADPH oxidase, a major protein in
the phagosome membrane of the leukocyte. The model predicts
that after activation of a neutrophil, an increase in the
activity of the hexose monophosphate shunt and the delivery of
myeloperoxidase into the phagosome results in oscillations in
oxygen and NAD(P)H concentration. The period of oscillation
changes from >200 s to 10-30 s. The model is consistent with
previously reported oscillations in cell metabolism and oxidant
production. Key features and predictions of the model were
confirmed experimentally. The requirement of the hexose
monophosphate pathway for 10 s oscillations was verified using
6-aminonicotinamide and dexamethasone, which are inhibitors of
glucose-6-phosphate dehydrogenase. The role of the NADPH
oxidase in promoting oscillations was confirmed by
dose-response studies of the effect of diphenylene iodonium, an
inhibitor of the NADPH oxidase. Moreover, the model predicted
an increase in the amplitude of NADPH oscillations in the
presence of melatonin, which was confirmed experimentally.
Successful computer modeling of complex chemical dynamics
within cells and their chemical perturbation will enhance our
ability to identify new antiinflammatory compounds.

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