On the stoichiometry of oxygen metabolism in polymorphonuclear leukocytes

doi:10.1016/S0006-291X(81)80084-8

Biochemical and Biophysical Research Communications

Volume 100, Issue 1, 15 May 1981, Pages 212-218

https://doi.org/10.1016/S0006-291X(81)80084-8 Get rights and content

Summary

The stoichiometry of oxygen uptake to superoxide output has been examined in neutrophilic polymorphonuclear leukocytes which have been stimulated by a particulate (serum-treated-zymosan) and a soluble (N-formylmethionyl-leucyl-phenylalanine) agent.

It has been shown that superoxide production by neutrophils does not necessarily accompany oxygen uptake during phagocytosis. Substantial superoxide-stimulating-activity (possibly complement fragment C3b) is derived from serum which has been stored at −20° but not from serum stored at 4°. N-formylmethionyl-leucyl-phenylalanine stimulates a much higher conversion of oxygen to superoxide than does serum-treated-zymosan.

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Infiltrating phagocytes generate superoxide anion (O₂⁻) and prostaglandin (PG) at sites of inflammation. Thus PG-O₂⁻ interactions may be important to the initiation and control of inflammation. PGE₁, PGE₂, and PGD₂ inhibit O₂⁻ generation (as measured by superoxide dismutase-inhibitable reduction of ferricytochrome c) in a dose-dependent manner (10⁻⁶–10⁻⁹M) when human peripheral blood polymorphonuclear leucocytes (PMN) are stimulated with 10⁻⁷M of the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). These PG did not alter O₂⁻ generation when PMN were stimulated with 0.1 μg/ml phorbol myristate acetate (PMA) or 1 mg/ml serum-treated zymosan (STZ). Increments of cyclic AMP (cAMP) (peak: fourfold) in PGE₁, PGE₂, and PGD₂ treated PMN stimulated with PMA or STZ (in which O₂⁻ was not reduced) were similar to those in PG-treated PMN stimulated with FMLP (in which O₂⁻ was reduced markedly). High concentrations of theophylline and dibutyryl cAMP reduced FMLP and STZ stimulated O₂⁻ generation but had no effect on PMA stimulation, suggesting that the stimuli induce different sensitivities to the effects of cellular cAMP. PGF_2α had little effect on O₂⁻ generation or cAMP levels regardless of the stimulus. PGE₁ did not inhibit binding of FML(³H)P to PMN and did not scavenge O₂⁻ anions. Therefore the effect of PG on O₂⁻ production is dependent on the specific stimulator and an increased concentration of cAMP in activated PMN is by itself not sufficient to limit O₂⁻ generation induced by all stimuli.
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On the stoichiometry of oxygen metabolism in polymorphonuclear leukocytes

Summary

J. Biol. Chem.

Biochem. Biophys. Res. Comm.

Biochim. Biophys. Acta

FEBS Lett.

Am. J. Physiol.

Nature

Semin. Hematol.

J. Clin. Invest.

J. Exp. Med.

J. Lab. Clin. Med.

J. Clin. Invest.