Abstract
We explored the relationship between phagocytosis and the triggering of oxidative metabolism using resident, lipopolysaccharide (LPS)-elicited, and bacille Calmette-Guerin (BCG)-activated murine peritoneal macrophages. Sheep erythrocytes (E) coated with IgG [E(IgG)], E coated with IgM and complement [E(IgM)C], and E treated with 1% glutaraldehyde (GE) were used as stimuli. All three types of macrophages released superoxide anion (O2-) during phagocytosis of E(IgG). All macrophage types phagocytosed E(IgM)C and GE but none were stimulated to release O2- during phagocytosis of these particles. Vigorous consumption of oxygen was also stimulated by the ingestion of E(IgG) but not by ingestion of E(IgM)C or GE. E(IgM)C did not scavenge the O2- released from macrophages during phagocytosis of E(IgG) or during exposure to phorbol myristate acetate, and further addition of IgG anti-E antibody to E(IgM)C or GE permitted optimal stimulation of macrophage O2- release by these particles. The capacity of macrophages to ingest E(IgM)C and GE without stimulating the respiratory burst raises the possibility that clearance of particulate matter not opsonized with specific IgG might be achieved without stimulation of the release of toxic oxygen metabolites, and, therefore, without the risk of oxidative damage to the phagocytic cell or surrounding tissue.
Full Text
The Full Text of this article is available as a PDF (943.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baehner R. L., Boxer L. A., Allen J. M., Davis J. Autooxidation as a basis for altered function by polymorphonuclear leukocytes. Blood. 1977 Aug;50(2):327–335. [PubMed] [Google Scholar]
- Bianco C., Griffin F. M., Jr, Silverstein S. C. Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation. J Exp Med. 1975 Jun 1;141(6):1278–1290. doi: 10.1084/jem.141.6.1278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capo C., Bongrand P., Benoliel A. M., Depieds R. Non-specific recognition in phagocytosis: ingestion of aldehyde-treated erythrocytes by rat peritoneal macrophages. Immunology. 1979 Mar;36(3):501–508. [PMC free article] [PubMed] [Google Scholar]
- Daimond R. D., Krzesicki R. Mechanisms of attachment of neutrophils to Candida albicans pseudohyphae in the absence of serum, and of subsequent damage to pseudohyphae by microbicidal processes of neutrophils in vitro. J Clin Invest. 1978 Feb;61(2):360–369. doi: 10.1172/JCI108946. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Danley D. L., Hilger A. E. Stimulation of oxidative metabolism in murine polymorphonuclear leukocytes by unopsonized fungal cells: evidence for a mannose-specific mechanism. J Immunol. 1981 Aug;127(2):551–556. [PubMed] [Google Scholar]
- Diamond R. D., Haudenschild C. C. Monocyte-mediated serum-independent damage to hyphal and pseudohyphal forms of Candida albicans in vitro. J Clin Invest. 1981 Jan;67(1):173–182. doi: 10.1172/JCI110010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drath D. B., Karnovsky M. L. Superoxide production by phagocytic leukocytes. J Exp Med. 1975 Jan 1;141(1):257–262. doi: 10.1084/jem.141.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edelson P. J., Erbs C. Biochemical and functional characteristics of the plasma membrane of macrophages from BCG-infected mice. J Immunol. 1978 May;120(5):1532–1536. [PubMed] [Google Scholar]
- Griffin F. M., Jr, Bianco C., Silverstein S. C. Characterization of the macrophage receptro for complement and demonstration of its functional independence from the receptor for the Fc portion of immunoglobulin G. J Exp Med. 1975 Jun 1;141(6):1269–1277. doi: 10.1084/jem.141.6.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gudewicz P. W., Beezhold D. H., Van Alten P., Molnar J. Lack of stimulation of post-phagocytic metabolic activities of polymorphonuclear leukocytes by fibronectin opsonized particles. J Reticuloendothel Soc. 1982 Aug;32(2):143–154. [PubMed] [Google Scholar]
- Hed J., Stendahl O. Differences in the ingestion mechanisms of IgG and C3b particles in phagocytosis by neutrophils. Immunology. 1982 Apr;45(4):727–736. [PMC free article] [PubMed] [Google Scholar]
- Johnston R. B., Jr, Chadwick D. A., Cohn Z. A. Priming of macrophages for enhanced oxidative metabolism by exposure to proteolytic enzymes. J Exp Med. 1981 Jun 1;153(6):1678–1683. doi: 10.1084/jem.153.6.1678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston R. B., Jr, Godzik C. A., Cohn Z. A. Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med. 1978 Jul 1;148(1):115–127. doi: 10.1084/jem.148.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston R. B., Jr, Klemperer M. R., Alper C. A., Rosen F. S. The enhancement of bacterial phagocytosis by serum. The role of complement components and two cofactors. J Exp Med. 1969 Jun 1;129(6):1275–1290. doi: 10.1084/jem.129.6.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston R. B., Jr, Lehmeyer J. E. Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. J Clin Invest. 1976 Apr;57(4):836–841. doi: 10.1172/JCI108359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston R. B., Jr, Lehmeyer J. E., Guthrie L. A. Generation of superoxide anion and chemiluminescence by human monocytes during phagocytosis and on contact with surface-bound immunoglobulin G. J Exp Med. 1976 Jun 1;143(6):1551–1556. doi: 10.1084/jem.143.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan G. Differences in the mode of phagocytosis with Fc and C3 receptors in macrophages. Scand J Immunol. 1977;6(8):797–807. doi: 10.1111/j.1365-3083.1977.tb02153.x. [DOI] [PubMed] [Google Scholar]
- Kay M. M. Mechanism of removal of senescent cells by human macrophages in situ. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3521–3525. doi: 10.1073/pnas.72.9.3521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Loike J. D., Silverstein S. C. A fluorescence quenching technique using trypan blue to differentiate between attached and ingested glutaraldehyde-fixed red blood cells in phagocytosing murine macrophages. J Immunol Methods. 1983 Feb 25;57(1-3):373–379. doi: 10.1016/0022-1759(83)90097-2. [DOI] [PubMed] [Google Scholar]
- Lutz H. U., Wipf G. Naturally occurring autoantibodies to skeletal proteins from human red blood cells. J Immunol. 1982 Apr;128(4):1695–1699. [PubMed] [Google Scholar]
- Mantovani B. Phagocytosis of immune complexes mediated by IgM and C3 receptors by macrophages from mice treated with glycogen. J Immunol. 1981 Jan;126(1):127–130. [PubMed] [Google Scholar]
- Mantovani B., Rabinovitch M., Nussenzweig V. Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG). J Exp Med. 1972 Apr 1;135(4):780–792. doi: 10.1084/jem.135.4.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morland B., Kaplan G. Macrophage activation in vivo and in vitro. Exp Cell Res. 1977 Sep;108(2):279–288. doi: 10.1016/s0014-4827(77)80035-9. [DOI] [PubMed] [Google Scholar]
- Munthe-Kaas A. C., Kaplan G., Seljelid R. On the mechanism of internalization of opsonized particles by rat Kupffer cells in vitro. Exp Cell Res. 1976 Nov;103(1):201–212. doi: 10.1016/0014-4827(76)90256-1. [DOI] [PubMed] [Google Scholar]
- Murray H. W., Cohn Z. A. Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation. J Exp Med. 1980 Dec 1;152(6):1596–1609. doi: 10.1084/jem.152.6.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray H. W. Interaction of Leishmania with a macrophage cell line. Correlation between intracellular killing and the generation of oxygen intermediates. J Exp Med. 1981 Jun 1;153(6):1690–1695. doi: 10.1084/jem.153.6.1690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nathan C. F., Root R. K. Hydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering. J Exp Med. 1977 Dec 1;146(6):1648–1662. doi: 10.1084/jem.146.6.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newburger P. E., Pagano J. S., Greenberger J. S., Karpas A., Cohen H. J. Dissociation of opsonized particle phagocytosis and respiratory burst activity in an Epstein-Barr virus-infected myeloid cell line. J Cell Biol. 1980 Jun;85(3):549–557. doi: 10.1083/jcb.85.3.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newman S. L., Henson J. E., Henson P. M. Phagocytosis of senescent neutrophils by human monocyte-derived macrophages and rabbit inflammatory macrophages. J Exp Med. 1982 Aug 1;156(2):430–442. doi: 10.1084/jem.156.2.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newman S. L., Johnston R. B., Jr Role of binding through C3b and IgG in polymorphonuclear neutrophil function: studies with trypsin-generated C3b. J Immunol. 1979 Oct;123(4):1839–1846. [PubMed] [Google Scholar]
- Rabinovitch M. Attachment of modified erythrocytes to phagocytic cells in absence of serum. Proc Soc Exp Biol Med. 1967 Feb;124(2):396–399. doi: 10.3181/00379727-124-31749. [DOI] [PubMed] [Google Scholar]
- Roos D., Bot A. A., van Schaik M. L., de Boer M., Daha M. R. Interaction between human neutrophils and zymosan particles: the role of opsonins and divalent cations. J Immunol. 1981 Feb;126(2):433–440. [PubMed] [Google Scholar]
- Roos D., Weening R. S., Voetman A. A., van Schaik M. L., Bot A. A., Meerhof L. J., Loos J. A. Protection of phagocytic leukocytes by endogenous glutathione: studies in a family with glutathione reductase deficiency. Blood. 1979 May;53(5):851–866. [PubMed] [Google Scholar]
- Sasada M., Johnston R. B., Jr Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. J Exp Med. 1980 Jul 1;152(1):85–98. doi: 10.1084/jem.152.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stossel T. P. Evaluation of opsonic and leukocyte function with a spectrophotometric test in patients with infection and with phagocytic disorders. Blood. 1973 Jul;42(1):121–130. [PubMed] [Google Scholar]
- Stubbs M., Kühner A. V., Glass E. A., David J. R., Karnovsky M. L. Metabolic and functonal studies on activated mouse macrophages. J Exp Med. 1973 Feb 1;137(2):537–542. doi: 10.1084/jem.137.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suzuki H., Kurita T., Kakinuma K. Effects of neuraminidase on O2 consumption and release of O2 and H2O2 from phagocytosing human polymorphonuclear leukocytes. Blood. 1982 Aug;60(2):446–453. [PubMed] [Google Scholar]
- Tsan M. F., Douglass K. H., McIntyre P. A. Hydrogen peroxide production and killing of Staphylococcus aureus by human polymorphonuclear leukocytes. Blood. 1977 Mar;49(3):437–444. [PubMed] [Google Scholar]
- Tsan M., McIntyre P. A. The requirement for membrane sialic acid in the stimulation of superoxide production during phagocytosis by human polymorphonuclear leukocytes. J Exp Med. 1976 Jun 1;143(6):1308–1316. doi: 10.1084/jem.143.6.1308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson C. B., Tsai V., Remington J. S. Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens. J Exp Med. 1980 Feb 1;151(2):328–346. doi: 10.1084/jem.151.2.328. [DOI] [PMC free article] [PubMed] [Google Scholar]