Abstract
The ability of macrophages to catabolize antigens is relevant both as a means to process complex antigens before presentation to T cells and as a way to down-regulate immune responses by destroying the antigenicity of polypeptides. With these considerations in mind, we investigated the regulation of macrophage catabolic activity by lipopolysaccharide (LPS). Catabolic activity was quantitated by following the distribution and molecular form of 125I-labeled surface components of heat-killed Listeria monocytogenes after their uptake by macrophages. We compared the catabolic activity of macrophages from peritoneal exudates of mice injected intraperitoneally with saline or LPS and found that LPS-elicited macrophages displayed a greatly enhanced (threefold) rate of catabolism. This increase in catabolic activity peaked 3 days after LPS injection and slowly declined thereafter, approaching a base-line level after 3 weeks. The enhancement of catabolic activity was under Lps gene control. Macrophages that were elicited 3 days after intraperitoneal injection of LPS rapidly destroyed the antigenicity of bacterial antigens, expressed low levels of Ia molecules, and processed and presented antigen slowly when tested as antigen-presenting cells in vitro. We also showed that an injection of LPS before infection with L. monocytogenes resulted in diminished development of T-cell reactivity to this organism. These results suggest that LPS elicits a macrophage population specialized for antigen degradation functions, with negative regulatory effects on the induction of specific immune responses.
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Selected References
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- Allen P. M., Beller D. I., Braun J., Unanue E. R. The handling of Listeria monocytogenes by macrophages: the search for an immunogenic molecule in antigen presentation. J Immunol. 1984 Jan;132(1):323–331. [PubMed] [Google Scholar]
- Bennett W. E., Cohn Z. A. The isolation and selected properties of blood monocytes. J Exp Med. 1966 Jan 1;123(1):145–160. doi: 10.1084/jem.123.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- COHN Z. A., BENSON B. THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY. J Exp Med. 1965 Jan 1;121:153–170. doi: 10.1084/jem.121.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cummings N. P., Pabst M. J., Johnston R. B., Jr Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide. J Exp Med. 1980 Dec 1;152(6):1659–1669. doi: 10.1084/jem.152.6.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farr A. G., Kiely J. M., Unanue E. R. Macrophage-T cell interactions involving Listeria monocytogenes--role of the H-2 gene complex. J Immunol. 1979 Jun;122(6):2395–2404. [PubMed] [Google Scholar]
- Farr A. G., Wechter W. J., Kiely J. M., Unanue E. R. Induction of cytocidal macrophages after in vitro interactions between Listeria-immune T cells and macrophages--role of H-2. J Immunol. 1979 Jun;122(6):2405–2412. [PubMed] [Google Scholar]
- GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galleli A., Le Garrec Y., Chedid L. Increased resistance and depressed delayed-type hypersensitivity to Listeria monocytogenes induced by pretreatment with lipopolysaccharide. Infect Immun. 1981 Jan;31(1):88–94. doi: 10.1128/iai.31.1.88-94.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hodes R. J., Ahmann G. B., Hathcock K. S., Dickler H. B., Singer A. Cellular and genetic control of antibody responses in vitro. IV. Expression of Ia antigens on accessory cells required for responses to soluble antigens including a response under Ir gene control. J Immunol. 1978 Oct;121(4):1501–1509. [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]
- 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]
- PARANT M., BOYER F., CHEDID L. AUGMENTATION DE LA R'ESISTANCE AUX INFECTIONS CONS'ECUTIVE 'A UNE INJECTION D'ENDOTOXINE. MISE EN 'EVIDENCE DU M'ECANISME PAR L'ASSOCIATION DE SULFAMIDE. C R Hebd Seances Acad Sci. 1965 Mar 1;260:2630–2633. [PubMed] [Google Scholar]
- Parant M. A., Parant F. J., Chedid L. A. Enhancement of resistance to infections by endotoxin-induced serum factor from Mycobacterium bovis BCG-infected mice. Infect Immun. 1980 Jun;28(3):654–659. doi: 10.1128/iai.28.3.654-659.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rao A., Faas S. J., Miller L. J., Riback P. S., Cantor H. Lysis of inducer T cell clones by activated macrophages and macrophage-like cell lines. J Exp Med. 1983 Oct 1;158(4):1243–1258. doi: 10.1084/jem.158.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [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]
- Silverstein S. C., Steinman R. M., Cohn Z. A. Endocytosis. Annu Rev Biochem. 1977;46:669–722. doi: 10.1146/annurev.bi.46.070177.003321. [DOI] [PubMed] [Google Scholar]
- WARAVDEKAR V. S., SASLAW L. D. A sensitive colorimetric method for the estimation of 2-deoxy sugars with the use of the malonaldehyde-thiobarbituric acid reaction. J Biol Chem. 1959 Aug;234(8):1945–1950. [PubMed] [Google Scholar]
- Watson J., Riblet R. Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones to lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1147–1161. doi: 10.1084/jem.140.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilton J. M., Rosenstreich D. L., Oppenheim J. J. Activation of guinea pig macrophages by bacterial lipopolysaccharide requires bone marrow-derived lymphocytes. J Immunol. 1975 Jan;114(1 Pt 2):388–393. [PubMed] [Google Scholar]
- Ziegler H. K., Orlin C. A. Analysis of Listeria monocytogenes antigens with monoclonal antibodies. Clin Invest Med. 1984;7(4):239–242. [PubMed] [Google Scholar]
- Ziegler H. K., Staffileno L. K., Wentworth P. Modulation of macrophage Ia-expression by lipopolysaccharide. I. Induction of Ia expression in vivo. J Immunol. 1984 Oct;133(4):1825–1835. [PubMed] [Google Scholar]
- Ziegler H. K., Unanue E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):175–178. doi: 10.1073/pnas.79.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziegler K., Unanue E. R. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. J Immunol. 1981 Nov;127(5):1869–1875. [PubMed] [Google Scholar]
- Ziegler K., Unanue E. R. The specific binding of Listeria monocytogenes-immune T lymphocytes to macrophages. I. Quantitation and role of H-2 gene products. J Exp Med. 1979 Nov 1;150(5):1143–1160. doi: 10.1084/jem.150.5.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
