Abstract
Immune sensitization of spleen cells was required to generate lymphokines (LK) that activated thioglycolate-elicited peritoneal macrophages (thio MACs) to respond via both oxygen-dependent and oxygen-independent systems. LK produced by incubating spleen cells from immunized A/J and LAF mice with concanavalin A stimulated a response by thio MACs to phorbol-12-myristate-13-acetate (PMA)-induced chemiluminescence and activated these cells to inhibit intracellular Chlamydia psittaci replication. Concanavalin A-incubated spleen cell preparations from unimmunized animals stimulated neither PMA-induced chemiluminescence nor antichlamydial activity. Activated thio MACs demonstrated a rapid chemiluminescence response to the intracellular protozoan Toxoplasma gondii, but C. psittaci did not induce chemiluminescence in LK-activated thio MACs, although cells exposed to C. psittaci retained their responsiveness to PMA-induced chemiluminescence. The PMA-induced response was inhibited by the addition of exogenous superoxide dismutase and catalase and was therefore related to the production of superoxide anion (O2 . -) and H2O2 by these cells. LK preparations incubated at 56 degrees C before macrophage treatment retained antichlamydial activity, but heated preparations no longer stimulated thio MACs to respond in the chemiluminescence assay. These data provide evidence that macrophage oxygen-dependent and oxygen-independent systems are simultaneously activated by LK, and these preparations comprise at least two distinct activities. The portion responsible for activating oxygen-dependent systems (PMA-induced chemiluminescence) is heat labile, whereas the portion responsible for activating oxygen-independent systems is heat stable. It is the latter system that results in restriction of chlamydial growth and in vitro parasite persistence.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams D. O., Johnson W. J., Marino P. A. Mechanisms of target recognition and destruction in macrophage-mediated tumor cytotoxicity. Fed Proc. 1982 Apr;41(6):2212–2221. [PubMed] [Google Scholar]
- Allen R. C., Stjernholm R. L., Steele R. H. 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. doi: 10.1016/0006-291x(72)90545-1. [DOI] [PubMed] [Google Scholar]
- Boraschi D., Meltzer M. S. Macrophage activation for tumor cytotoxicity: genetic variation in macrophage tumoricidal capacity among mouse strains. Cell Immunol. 1979 Jun;45(1):188–194. doi: 10.1016/0008-8749(79)90375-7. [DOI] [PubMed] [Google Scholar]
- Byrne G. I., Faubion C. L. Lymphokine-mediated microbistatic mechanisms restrict Chlamydia psittaci growth in macrophages. J Immunol. 1982 Jan;128(1):469–474. [PubMed] [Google Scholar]
- Chinchilla M., Frenkel J. K. Mediation of immunity to intracellular infection (Toxoplasma and Besnoitia) within somatic cells. Infect Immun. 1978 Mar;19(3):999–1012. doi: 10.1128/iai.19.3.999-1012.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen M. S., Ryan J. L., Root R. K. The oxidative metabolism of thioglycollate-elicited mouse peritoneal macrophages: the relationship between oxygen, superoxide and hydrogen peroxide and the effect of monolayer formation. J Immunol. 1981 Sep;127(3):1007–1011. [PubMed] [Google Scholar]
- Cohen M. S., Taffet S. M., Adams D. O. The relationship between competence for secretion of H2O2 and completion of tumor cytotoxicity by BCG-elicited murine macrophages. J Immunol. 1982 Apr;128(4):1781–1785. [PubMed] [Google Scholar]
- David J. R. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966 Jul;56(1):72–77. doi: 10.1073/pnas.56.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- David J. R. Macrophage activation by lymphocyte mediators. Fed Proc. 1975 Jul;34(8):1730–1736. [PubMed] [Google Scholar]
- DeChatelet L. R., Shirley P. S. Chemiluminescence of human neutrophils induced by soluble stimuli: effect of divalent cations. Infect Immun. 1982 Jan;35(1):206–212. doi: 10.1128/iai.35.1.206-212.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dumont A. Correlative ultrastructural and functional study of hamster peritoneal macrophage activation in vitro by lymphokines. J Reticuloendothel Soc. 1978 Oct;24(4):317–332. [PubMed] [Google Scholar]
- Elsbach P., Weiss J., Franson R. C., Beckerdite-Quagliata S., Schneider A., Harris L. Separation and purification of a potent bactericidal/permeability-increasing protein and a closely associated phospholipase A2 from rabbit polymorphonuclear leukocytes. Observations on their relationship. J Biol Chem. 1979 Nov 10;254(21):11000–11009. [PubMed] [Google Scholar]
- Gabig T. G., Babior B. M. The killing of pathogens by phagocytes. Annu Rev Med. 1981;32:313–326. doi: 10.1146/annurev.me.32.020181.001525. [DOI] [PubMed] [Google Scholar]
- Gallily R., Eliahu H. Mechanism and specificity of macrophage-mediated cytotoxity. Cell Immunol. 1976 Aug;25(2):245–255. doi: 10.1016/0008-8749(76)90115-5. [DOI] [PubMed] [Google Scholar]
- González P. H., Lampuri J. S., Coto C. E., Laguens R. P. In vitro infection of murine macrophages with Junin virus. Infect Immun. 1982 Jan;35(1):356–358. doi: 10.1128/iai.35.1.356-358.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hatch T. P. Competition between Chlamydia psittaci and L cells for host isoleucine pools: a limiting factor in chlamydial multiplication. Infect Immun. 1975 Jul;12(1):211–220. doi: 10.1128/iai.12.1.211-220.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horwitz M. A., Silverstein S. C. Activated human monocytes inhibit the intracellular multiplication of Legionnaires' disease bacteria. J Exp Med. 1981 Nov 1;154(5):1618–1635. doi: 10.1084/jem.154.5.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kniep E. M., Domzig W., Lohmann-Matthes M. L., Kickhöfen B. Partial purification and chemical characterization of macrophage cytotoxicity factor (MCF, MAF) and its separation from migration inhibitory factor (MIF). J Immunol. 1981 Aug;127(2):417–422. [PubMed] [Google Scholar]
- LITWIN J. The growth cycle of the psittacosis group of micro-organisms. J Infect Dis. 1959 Sep-Oct;105:129–160. doi: 10.1093/infdis/105.2.129. [DOI] [PubMed] [Google Scholar]
- Lee C. K. Factors affecting the rate as which a trachoma strain of Chlamydia trachomatis establishes persistent infections in mouse fibroblasts (McCoy cells). Infect Immun. 1981 Sep;33(3):954–957. doi: 10.1128/iai.33.3.954-957.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee C. K., Moulder J. W. Persistent infection of mouse fibroblasts (McCoy cells) with a trachoma strain of Chlamydia trachomatis. Infect Immun. 1981 May;32(2):822–829. doi: 10.1128/iai.32.2.822-829.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrer R. I., Ladra K. M., Hake R. B. Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes. Infect Immun. 1975 Jun;11(6):1226–1234. doi: 10.1128/iai.11.6.1226-1234.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrer R. I., Szklarek D., Selsted M. E., Fleischmann J. Increased content of microbicidal cationic peptides in rabbit alveolar macrophages elicited by complete Freund adjuvant. Infect Immun. 1981 Sep;33(3):775–778. doi: 10.1128/iai.33.3.775-778.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MACKANESS G. B. Cellular resistance to infection. J Exp Med. 1962 Sep 1;116:381–406. doi: 10.1084/jem.116.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandell G. L. Bactericidal activity of aerobic and anaerobic polymorphonuclear neutrophils. Infect Immun. 1974 Feb;9(2):337–341. doi: 10.1128/iai.9.2.337-341.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meshnick S. R., Eaton J. W. Leishmanial superoxide dismutase: a possible target for chemotherapy. Biochem Biophys Res Commun. 1981 Oct 15;102(3):970–976. doi: 10.1016/0006-291x(81)91633-8. [DOI] [PubMed] [Google Scholar]
- Moulder J. W., Zeichner S. L., Levy N. J. Association between resistance to superinfection and patterns of surface protein labeling in mouse fibroblasts (L cells) persistently infected with Chlamydia psittaci. Infect Immun. 1982 Mar;35(3):834–839. doi: 10.1128/iai.35.3.834-839.1982. [DOI] [PMC free article] [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., Cohn Z. A. Mononuclear phagocyte antimicrobial and antitumor activity: the role of oxygen intermediates. J Invest Dermatol. 1980 May;74(5):285–288. doi: 10.1111/1523-1747.ep12543457. [DOI] [PubMed] [Google Scholar]
- Nacy C. A., Leonard E. J., Meltzer M. S. Macrophages in resistance to rickettsial infections: characterization of lymphokines that induce rickettsiacidal activity in macrophages. J Immunol. 1981 Jan;126(1):204–207. [PubMed] [Google Scholar]
- Nacy C. A., Meltzer M. S. Macrophages in resistance to rickettsial infection: macrophage activation in vitro for killing of Rickettsia tsutsugamushi. J Immunol. 1979 Dec;123(6):2544–2549. [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]
- Nathan C. F. Secretion of oxygen intermediates: role in effector functions of activated macrophages. Fed Proc. 1982 Apr;41(6):2206–2211. [PubMed] [Google Scholar]
- Nathan C. F., Silverstein S. C., Brukner L. H., Cohn Z. A. Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med. 1979 Jan 1;149(1):100–113. doi: 10.1084/jem.149.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nathan C., Nogueira N., Juangbhanich C., Ellis J., Cohn Z. Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi. J Exp Med. 1979 May 1;149(5):1056–1068. doi: 10.1084/jem.149.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nielson E. G., Phillips S. M., Jimenez S. Lymphokine modulation of fibroblast proliferation. J Immunol. 1982 Mar;128(3):1484–1486. [PubMed] [Google Scholar]
- North R. J. The concept of the activated macrophage. J Immunol. 1978 Sep;121(3):806–809. [PMC free article] [PubMed] [Google Scholar]
- Schoenholz W. K. Studies on Bedsonia latency. II. Effect of immune lymphocytes and of rabbit-anti-lymphocyte globulin (RAMLG) on infected macrophages exposed to increased incubation temperature in vitro. Z Immunitatsforsch Allerg Klin Immunol. 1970 May;139(4):359–371. [PubMed] [Google Scholar]
- Shaw D. R., Griffin F. M., Jr Thioglycollate-elicited mouse peritoneal macrophages are less efficient than resident macrophages in antibody-dependent cell-mediated cytolysis. J Immunol. 1982 Jan;128(1):433–440. [PubMed] [Google Scholar]
- Sorg C., Klinkert W. Chemical characterization of products of activated lymphocytes. Fed Proc. 1978 Nov;37(13):2748–2753. [PubMed] [Google Scholar]
- Spitalny G. L. Dissociation of bactericidal activity from other functions of activated macrophages in exudates induced by thioglycolate medium. Infect Immun. 1981 Oct;34(1):274–284. doi: 10.1128/iai.34.1.274-284.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss J., Elsbach P., Olsson I., Odeberg H. Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem. 1978 Apr 25;253(8):2664–2672. [PubMed] [Google Scholar]
- Weiss J., Victor M., Stendhal O., Elsbach P. Killing of gram-negative bacteria by polymorphonuclear leukocytes: role of an O2-independent bactericidal system. J Clin Invest. 1982 Apr;69(4):959–970. doi: 10.1172/JCI110535. [DOI] [PMC free article] [PubMed] [Google Scholar]