Termination of the respiratory burst in human neutrophils.
PDF (2.3M)
Journal: 1978/August - Journal of Clinical Investigation
ISSN: 0021-9738
Abstract:
Recent evidence has suggested that a particulate O(2) (-)-forming system is responsible for the respiratory burst in activated neutrophils. The respiratory burst is normally a transient event, lasting only 30-60 min. To investigate the mechanism by which the burst is terminated, we examined the O(2) (-)-forming activity of neutrophil particles as a function of time in the presence and absence of agents known to affect the function of intact cells. Measurements of the O(2) (-)-forming capacity of the particles against time of exposure of neutrophils to opsonized zymosan, a potent stimulating agent, revealed a rapid fall in activity when exposure was continued beyond 3 min. Exposure to zymosan under conditions in which the myeloperoxidase system was inactive (i.e., in the presence of myeloperoxidase inhibitors, or in the absence of oxygen) resulted in a substantial increase in the initial O(2) (-)-forming activity of particles from the zymosan-treated cells, but did not prevent the sharp fall in activity seen when zymosan exposure exceeded 10 min. The fall in activity was, however, prevented when activation took place in the presence of cytochalasin B (1.5 mug/ml), an agent thought to act largely by paralyzing the neutrophil through an interaction with its microfilament network.We conclude from these findings that the termination of the respiratory burst results at least in part from the inactivation of the particulate O(2) (-)-forming system. This inactivation involves at least two processes which probably act simultaneously. One is the destruction of the system through the action of myeloperoxidase. The other appears to require active cell motility and is independent of oxygen. The current view holds that the O(2) (-)-forming system of the neutrophil is located in the plasma membrane. It may be that the second process involves the internalization and degradation of this membrane-bound system.
Open in
PUBMED | DOI | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(39)
References
(46)
Chemicals
(4)
Organisms
(1)
Processes
(3)
Anatomy
(1)
Similar articles
Articles by the same authors
Discussion board
J Clin Invest 61(5): 1176-1185
PMID: 207730

Termination of the Respiratory Burst in Human Neutrophils

Abstract

Recent evidence has suggested that a particulate O2-forming system is responsible for the respiratory burst in activated neutrophils. The respiratory burst is normally a transient event, lasting only 30-60 min. To investigate the mechanism by which the burst is terminated, we examined the O2-forming activity of neutrophil particles as a function of time in the presence and absence of agents known to affect the function of intact cells. Measurements of the O2-forming capacity of the particles against time of exposure of neutrophils to opsonized zymosan, a potent stimulating agent, revealed a rapid fall in activity when exposure was continued beyond 3 min. Exposure to zymosan under conditions in which the myeloperoxidase system was inactive (i.e., in the presence of myeloperoxidase inhibitors, or in the absence of oxygen) resulted in a substantial increase in the initial O2-forming activity of particles from the zymosan-treated cells, but did not prevent the sharp fall in activity seen when zymosan exposure exceeded 10 min. The fall in activity was, however, prevented when activation took place in the presence of cytochalasin B (1.5 μg/ml), an agent thought to act largely by paralyzing the neutrophil through an interaction with its microfilament network.

We conclude from these findings that the termination of the respiratory burst results at least in part from the inactivation of the particulate O2-forming system. This inactivation involves at least two processes which probably act simultaneously. One is the destruction of the system through the action of myeloperoxidase. The other appears to require active cell motility and is independent of oxygen. The current view holds that the O2-forming system of the neutrophil is located in the plasma membrane. It may be that the second process involves the internalization and degradation of this membrane-bound system.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
icon of scanned page 1176
1176
icon of scanned page 1177
1177
icon of scanned page 1178
1178
icon of scanned page 1179
1179
icon of scanned page 1180
1180
icon of scanned page 1181
1181
icon of scanned page 1182
1182
icon of scanned page 1183
1183
icon of scanned page 1184
1184
icon of scanned page 1185
1185

Images in this article

Image
Image
on p.1182
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Klebanoff SJ. Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes. Semin Hematol. 1975 Apr;12(2):117–142. [PubMed] [Google Scholar]
  • Cheson BD, Curnette JT, Babior BM. The oxidative killing mechanisms of the neutrophil. Prog Clin Immunol. 1977;3:1–65. [PubMed] [Google Scholar]
  • SBARRA AJ, KARNOVSKY ML. The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes. J Biol Chem. 1959 Jun;234(6):1355–1362. [PubMed] [Google Scholar]
  • Weening RS, Roos D, Loos JA. Oxygen consumption of phagocytizing cells in human leukocyte and granulocyte preparations: a comparative study. J Lab Clin Med. 1974 Apr;83(4):570–577. [PubMed] [Google Scholar]
  • OREN R, FARNHAM AE, SAITO K, MILOFSKY E, KARNOVSKY ML. Metabolic patterns in three types of phagocytizing cells. J Cell Biol. 1963 Jun;17:487–501.[PMC free article] [PubMed] [Google Scholar]
  • Curnutte JT, Babior BM. Biological defense mechanisms. The effect of bacteria and serum on superoxide production by granulocytes. J Clin Invest. 1974 Jun;53(6):1662–1672.[PMC free article] [PubMed] [Google Scholar]
  • Babior BM, Kipnes RS, Curnutte JT. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744.[PMC free article] [PubMed] [Google Scholar]
  • Weening RS, Wever R, Roos D. Quantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes. J Lab Clin Med. 1975 Feb;85(2):245–252. [PubMed] [Google Scholar]
  • Johnston RB, Jr, Keele BB, Jr, Misra HP, Lehmeyer JE, Webb LS, Baehner RL, RaJagopalan KV. The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes. J Clin Invest. 1975 Jun;55(6):1357–1372.[PMC free article] [PubMed] [Google Scholar]
  • Root RK, Metcalf J, Oshino N, Chance B. H2O2 release from human granulocytes during phagocytosis. I. Documentation, quantitation, and some regulating factors. J Clin Invest. 1975 May;55(5):945–955.[PMC free article] [PubMed] [Google Scholar]
  • Homan-Müller JW, Weening RS, Roos D. Production of hydrogen peroxide by phagocytizing human granulocytes. J Lab Clin Med. 1975 Feb;85(2):198–207. [PubMed] [Google Scholar]
  • Babior BM, Curnutte JT, McMurrich BJ. The particulate superoxide-forming system from human neutrophils. Properties of the system and further evidence supporting its participation in the respiratory burst. J Clin Invest. 1976 Oct;58(4):989–996.[PMC free article] [PubMed] [Google Scholar]
  • Reed PW. Glutathione and the hexose monophosphate shunt in phagocytizing and hydrogen peroxide-treated rat leukocytes. J Biol Chem. 1969 May 10;244(9):2459–2464. [PubMed] [Google Scholar]
  • Baehner RL, Murrmann SK, Davis J, Johnston RB., Jr The role of superoxide anion and hydrogen peroxide in phagocytosis-associated oxidative metabolic reactions. J Clin Invest. 1975 Sep;56(3):571–576.[PMC free article] [PubMed] [Google Scholar]
  • Malawista SE, Bodel PT. The dissociation by colchicine of phagocytosis from increased oxygen consumption in human leukocytes. J Clin Invest. 1967 May;46(5):786–796.[PMC free article] [PubMed] [Google Scholar]
  • Quie PG, White JG, Holmes B, Good RA. In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest. 1967 Apr;46(4):668–679.[PMC free article] [PubMed] [Google Scholar]
  • Simmons SR, Karnovsky ML. Iodinating ability of various leukocytes and their bactericidal activity. J Exp Med. 1973 Jul 1;138(1):44–63.[PMC free article] [PubMed] [Google Scholar]
  • Curnutte JT, Babior BM. Effects of anaerobiosis and inhibitors on O2-production by human granulocytes. Blood. 1975 Jun;45(6):851–861. [PubMed] [Google Scholar]
  • Hohn DC, Lehrer RI. NADPH oxidase deficiency in X-linked chronic granulomatous disease. J Clin Invest. 1975 Apr;55(4):707–713.[PMC free article] [PubMed] [Google Scholar]
  • André-Schwartz J, Schwartz RS, Hirsch MS, Phillips SM, Black PH. Activation of leukemia viruses by graft-versus-host and mixed-lymphocyte-culture reactions: electron microscopic evidence of C-type particles. J Natl Cancer Inst. 1973 Aug;51(2):507–518. [PubMed] [Google Scholar]
  • Bretz U, Baggiolini M. Biochemical and morphological characterization of azurophil and specific granules of human neutrophilic polymorphonuclear leukocytes. J Cell Biol. 1974 Oct;63(1):251–269.[PMC free article] [PubMed] [Google Scholar]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  • Rosen H, Klebanoff SJ. Chemiluminescence and superoxide production by myeloperoxidase-deficient leukocytes. J Clin Invest. 1976 Jul;58(1):50–60.[PMC free article] [PubMed] [Google Scholar]
  • Klebanoff SJ, Hamon CB. Role of myeloperoxidase-mediated antimicrobial systems in intact leukocytes. J Reticuloendothel Soc. 1972 Aug;12(2):170–196. [PubMed] [Google Scholar]
  • Lindström A, Olsson B, Petterson G. Effect of azide on some spectral and kinetic properties of pig-plasma benzylamine oxidase. Eur J Biochem. 1974 Oct 1;48(1):237–243. [PubMed] [Google Scholar]
  • Gunnarsson PO, Nylén U, Petersson G. Inhibition of ceruloplasmin by inorganic anions. Eur J Biochem. 1972 Jun 9;27(3):572–577. [PubMed] [Google Scholar]
  • Speyer BE, Curzon G. The inhibition of caeruloplasmin by cyanide. Biochem J. 1968 Feb;106(4):905–911.[PMC free article] [PubMed] [Google Scholar]
  • Rotilio G, Bray RC, Fielden EM. A pulse radiolysis study of superoxide dismutase. Biochim Biophys Acta. 1972 May 12;268(2):605–609. [PubMed] [Google Scholar]
  • Hanlon DP, Shuman S. Copper ion binding and enzyme inhibitory properties of the antithyroid drug methimazole. Experientia. 1975 Sep 15;31(9):1005–1006. [PubMed] [Google Scholar]
  • Bardsley WG, Childs RE, Crabbe MJ. Inhibition of enzymes by metal ion-chelating reagents. The action of copper-chelating reagents on diamine oxidase. Biochem J. 1974 Jan;137(1):61–66.[PMC free article] [PubMed] [Google Scholar]
  • Heikkila RE, Cabbat FS, Cohen G. In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate. J Biol Chem. 1976 Apr 10;251(7):2182–2185. [PubMed] [Google Scholar]
  • Babior BM, Curnutte JT, Kipnes RS. Biological defense mechanisms. Evidence for the participation of superoxide in bacterial killing by xanthine oxidase. J Lab Clin Med. 1975 Feb;85(2):235–244. [PubMed] [Google Scholar]
  • Gregory EM, Fridovich I. Oxygen metabolism in Lactobacillus plantarum. J Bacteriol. 1974 Jan;117(1):166–169.[PMC free article] [PubMed] [Google Scholar]
  • Allen RC, Stjernholm RL, Steele RH. Evidence for the generation of an electronic excitation state(s) in human polymorphonuclear leukocytes and its participation in bactericidal activity. Biochem Biophys Res Commun. 1972 May 26;47(4):679–684. [PubMed] [Google Scholar]
  • Krinsky NI. Singlet excited oxygen as a mediator of the antibacterial action of leukocytes. Science. 1974 Oct 25;186(4161):363–365. [PubMed] [Google Scholar]
  • Maugh TH., 2nd Singlet oxygen: a unique microbicidal agent in cells. Science. 1973 Oct 5;182(4107):44–45. [PubMed] [Google Scholar]
  • Lin S, Spudich JA. Biochemical studies on the mode of action of cytochalasin B. Cytochalasin B binding to red cell membrane in relation to glucose transport. J Biol Chem. 1974 Sep 25;249(18):5778–5783. [PubMed] [Google Scholar]
  • COHN ZA, MORSE SI. Functional and metabolic properties of polymorphonuclear leucocytes. I. Observations on the requirements and consequences of particle ingestion. J Exp Med. 1960 May 1;111:667–687.[PMC free article] [PubMed] [Google Scholar]
  • Zigmond SH, Hirsch JG. Effects of cytochalasin B on polymorphonuclear leucocyte locomotion, phagocytosis and glycolysis. Exp Cell Res. 1972 Aug;73(2):383–393. [PubMed] [Google Scholar]
  • Becker EL, Davis AT, Estensen RD, Quie PG. Cytochalasin B. IV. Inhibition and stimulation of chemotaxis of rabbit and human polymorphonuclear leukocytes. J Immunol. 1972 Feb;108(2):396–402. [PubMed] [Google Scholar]
  • Davies P, Fox RI, Polyzonis M, Allison AC, Haswell AD. The inhibition of phagocytosis and facilitation of exocytosis in rabbit polymorphonuclear leukocytes by cytochalasin B. Lab Invest. 1973 Jan;28(1):16–22. [PubMed] [Google Scholar]
  • Davis AT, Estensen R, Quie PG. Cytochalasin B. 3. Inhibition of human polymorphonuclear leukocyte phagocytosis. Proc Soc Exp Biol Med. 1971 May;137(1):161–164. [PubMed] [Google Scholar]
  • Malawista SE, Gee JB, Bensch KG. Cytochalasin B reversibly inhibits phagocytosis: functional, metabolic, and ultrastructural effects in human blood leukocytes and rabbit alveolar macrophages. Yale J Biol Med. 1971 Dec;44(3):286–300.[PMC free article] [PubMed] [Google Scholar]
  • Ryan GB, Borysenko JZ, Karnovsky MJ. Factors affecting the redistribution of surface-bound concanavalin A on human polymorphonuclear leukocytes. J Cell Biol. 1974 Aug;62(2):351–365.[PMC free article] [PubMed] [Google Scholar]
  • Goldstein IM, Roos D, Kaplan HB, Weissmann G. Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis. J Clin Invest. 1975 Nov;56(5):1155–1163.[PMC free article] [PubMed] [Google Scholar]
  • Goldstein IM, Cerqueira M, Lind S, Kaplan HB. Evidence that the superoxide-generating system of human leukocytes is associated with the cell surface. J Clin Invest. 1977 Feb;59(2):249–254.[PMC free article] [PubMed] [Google Scholar]
Hematology Service, New England Medical Center Hospital, Boston, Massachusetts 02111
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111
Copyright notice
Abstract
Recent evidence has suggested that a particulate O2-forming system is responsible for the respiratory burst in activated neutrophils. The respiratory burst is normally a transient event, lasting only 30-60 min. To investigate the mechanism by which the burst is terminated, we examined the O2-forming activity of neutrophil particles as a function of time in the presence and absence of agents known to affect the function of intact cells. Measurements of the O2-forming capacity of the particles against time of exposure of neutrophils to opsonized zymosan, a potent stimulating agent, revealed a rapid fall in activity when exposure was continued beyond 3 min. Exposure to zymosan under conditions in which the myeloperoxidase system was inactive (i.e., in the presence of myeloperoxidase inhibitors, or in the absence of oxygen) resulted in a substantial increase in the initial O2-forming activity of particles from the zymosan-treated cells, but did not prevent the sharp fall in activity seen when zymosan exposure exceeded 10 min. The fall in activity was, however, prevented when activation took place in the presence of cytochalasin B (1.5 μg/ml), an agent thought to act largely by paralyzing the neutrophil through an interaction with its microfilament network.We conclude from these findings that the termination of the respiratory burst results at least in part from the inactivation of the particulate O2-forming system. This inactivation involves at least two processes which probably act simultaneously. One is the destruction of the system through the action of myeloperoxidase. The other appears to require active cell motility and is independent of oxygen. The current view holds that the O2-forming system of the neutrophil is located in the plasma membrane. It may be that the second process involves the internalization and degradation of this membrane-bound system.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.