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. 1994 Dec;102(Suppl 10):43–44. doi: 10.1289/ehp.94102s1043

Aspects of the release of superoxide by leukocytes, and a means by which this is switched off.

M L Karnovsky 1, A Bishop 1, V C Camerero 1, M A Paz 1, P Colepicolo 1, J M Ribeiro 1, P M Gallop 1
PMCID: PMC1567005  PMID: 7705303

Abstract

Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (O2-), it is possible that a component or components, might have been overlooked. Furthermore, O2- production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off O2- production by stimulated leukocytes. This article offers evidence that methoxatin (PQQ), a redox-cycling orthoquinone, might be involved in O2- production by leukocytes. This is based on the fact that inhibitors of O2- production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored O2- release. With respect to turning off cellular O2- release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked O2- release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo A., Boyhan A., West I., Thrasher A. J., Segal A. W. Reconstitution of neutrophil NADPH oxidase activity in the cell-free system by four components: p67-phox, p47-phox, p21rac1, and cytochrome b-245. J Biol Chem. 1992 Aug 25;267(24):16767–16770. [PubMed] [Google Scholar]
  2. Babior B. M. The respiratory burst oxidase. Adv Enzymol Relat Areas Mol Biol. 1992;65:49–95. doi: 10.1002/9780470123119.ch2. [DOI] [PubMed] [Google Scholar]
  3. Camarero V. C., Junqueira V. B., Colepicolo P., Karnovsky M. L., Mariano M. Epithelial macrophages secrete a deactivating factor for superoxide release. J Cell Physiol. 1990 Dec;145(3):481–487. doi: 10.1002/jcp.1041450313. [DOI] [PubMed] [Google Scholar]
  4. Cross A. R. Inhibitors of the leukocyte superoxide generating oxidase: mechanisms of action and methods for their elucidation. Free Radic Biol Med. 1990;8(1):71–93. doi: 10.1016/0891-5849(90)90147-b. [DOI] [PubMed] [Google Scholar]
  5. Cross A. R., Jones O. T. The effect of the inhibitor diphenylene iodonium on the superoxide-generating system of neutrophils. Specific labelling of a component polypeptide of the oxidase. Biochem J. 1986 Jul 1;237(1):111–116. doi: 10.1042/bj2370111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cross A. R. The inhibitory effects of some iodonium compounds on the superoxide generating system of neutrophils and their failure to inhibit diaphorase activity. Biochem Pharmacol. 1987 Feb 15;36(4):489–493. doi: 10.1016/0006-2952(87)90356-x. [DOI] [PubMed] [Google Scholar]
  7. Doussière J., Vignais P. V. Diphenylene iodonium as an inhibitor of the NADPH oxidase complex of bovine neutrophils. Factors controlling the inhibitory potency of diphenylene iodonium in a cell-free system of oxidase activation. Eur J Biochem. 1992 Aug 15;208(1):61–71. doi: 10.1111/j.1432-1033.1992.tb17159.x. [DOI] [PubMed] [Google Scholar]
  8. Kilpatrick L., Johnson J. L., Nickbarg E. B., Wang Z. M., Clifford T. F., Banach M., Cooperman B. S., Douglas S. D., Rubin H. Inhibition of human neutrophil superoxide generation by alpha 1-antichymotrypsin. J Immunol. 1991 Apr 1;146(7):2388–2393. [PubMed] [Google Scholar]
  9. Nakagawara A., Nathan C. F., Cohn Z. A. Hydrogen peroxide metabolism in human monocytes during differentiation in vitro. J Clin Invest. 1981 Nov;68(5):1243–1252. doi: 10.1172/JCI110370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rotrosen D., Yeung C. L., Leto T. L., Malech H. L., Kwong C. H. Cytochrome b558: the flavin-binding component of the phagocyte NADPH oxidase. Science. 1992 Jun 5;256(5062):1459–1462. doi: 10.1126/science.1318579. [DOI] [PubMed] [Google Scholar]
  11. Smidt C. R., Steinberg F. M., Rucker R. B. Physiologic importance of pyrroloquinoline quinone. Proc Soc Exp Biol Med. 1991 May;197(1):19–26. doi: 10.3181/00379727-197-43218. [DOI] [PubMed] [Google Scholar]
  12. Tsunawaki S., Nathan C. F. Macrophage deactivation. Altered kinetic properties of superoxide-producing enzyme after exposure to tumor cell-conditioned medium. J Exp Med. 1986 Oct 1;164(4):1319–1331. doi: 10.1084/jem.164.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]

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