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. 1971 May;8(5):801–814.

Studies on antimacrophage globulin*

H E Jasin, Dorothy Lennard, M Ziff
PMCID: PMC1712972  PMID: 5581066

Abstract

The immunosuppressive and anti-inflammatory properties of rabbit antirat macrophage (AMG) and rabbit antirat thymocyte globulin (ALG) have been compared. In vitro experiments showed that both AMG and ALG contained antibodies directed against rat thymocytes and macrophages. When AMG was absorbed with large numbers of thymocytes, the final product was found to lack agglutinating and cytotoxic antibodies against such cells. However, AMG was cytotoxic to rat peritoneal macrophages at a dilution of 1/512 while the ALG cytotoxic titre was 1/64. It was also shown that AMG was able to suppress phagocytosis by peritoneal mononuclear cells while ALG was ineffective.

The immunosuppressive activity of AMG and ALG when given at the time of induction of the immune response was studied in vivo. Rats were pretreated with the antisera prior to induction of Freund's adjuvant arthritis and immunization with sheep erythrocytes. Administration of ALG prior to induction of adjuvant arthritis resulted in complete inhibition of the disease while AMG treated rats developed arthritis. ALG treated rats produced almost no haemagglutinating antibody to sheep erythrocytes used as antigen while the AMG treated group developed titres not significantly different from the control group. When the same animals were rechallenged with sheep erythrocytes 5 weeks later the response of the AMG treated group was similar to that of controls, while the ALG treated animals developed a primary antibody response.

When the antisera were given to animals coinciding with the development of generalized arthritis in order to study their anti-inflammatory activity, AMG treated rats showed a small decrease in the severity of arthritis. ALG was much more effective in reducing the inflammatory signs of the disease and its suppressive effects lasted for 2 weeks after the last injection. The anti-inflammatory properties of ALG were also evident in the marked inhibition of the granuloma in the adjuvant-injected paw which paralleled the effects of treatment on the polyarthritis. Similarly, ALG treatment produced a severe depression of the delayed hypersensitivity response to tuberculin while AMG was ineffective.

The above results indicate that ALG is a strong anti-inflammatory and immunosuppressive agent while AMG has no immunosuppressive properties and is only a mild anti-inflammatory agent.

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Selected References

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

  1. Currey H. L., Ziff M. Suppression of adjuvant disease in the rat by heterologous antilymphocyte globulin. J Exp Med. 1968 Jan 1;127(1):185–203. doi: 10.1084/jem.127.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DAVID J. R., AL-ASKARI S., LAWRENCE H. S., THOMAS L. DELAYED HYPERSENSITIVITY IN VITRO. I. THE SPECIFICITY OF INHIBITION OF CELL MIGRATION BY ANTIGENS. J Immunol. 1964 Aug;93:264–273. [PubMed] [Google Scholar]
  3. Denman A. M., Denman E. J., Embling P. H. Changes in the life-span of circulating small lymphocytes in mice after treatment with anti-lymphocyte globulin. Lancet. 1968 Feb 17;1(7538):321–325. doi: 10.1016/s0140-6736(68)90791-5. [DOI] [PubMed] [Google Scholar]
  4. Field E. J., Hughes D. Anti-macrophage component of antilymphocytic serum. Lancet. 1969 Apr 26;1(7600):893–894. doi: 10.1016/s0140-6736(69)91945-x. [DOI] [PubMed] [Google Scholar]
  5. Granger G. A., Williams T. W. Lymphocyte cytotoxicity in vitro: activation and release of a cytotoxic factor. Nature. 1968 Jun 29;218(5148):1253–1254. doi: 10.1038/2181253a0. [DOI] [PubMed] [Google Scholar]
  6. HUMPHREY J. H. The mechanism of Arthus reactions. II. The role of polymorphonuclear leucocytes and platelets in reversed passive reactions in the guinea-pig. Br J Exp Pathol. 1955 Jun;36(3):283–289. [PMC free article] [PubMed] [Google Scholar]
  7. Huber H., Michlmayr G., Fudenberg H. H. The effect of anti-lymphocyte globulin on human monocytes in vitro. Clin Exp Immunol. 1969 Dec;5(6):607–617. [PMC free article] [PubMed] [Google Scholar]
  8. KOSUNEN T. U., WAKSMAN B. H., FLAX M. H., TIHEN W. S. Radioautographic study of cellular mechanisms in delayed hypersensitivity. I. Delayed reactions to tuberculin and purified proteins in the rat and guinea-pig. Immunology. 1963 May;6:276–290. [PMC free article] [PubMed] [Google Scholar]
  9. LOSPALLUTO J., CHEGORIANSKY J., LEWIS A., ZIFF M. Chromatographic properties of gamma globulin: behavior of serum gamma macroglobulins. J Clin Invest. 1960 Mar;39:473–480. doi: 10.1172/JCI104061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lawrence J. S., Barnett E. V., Craddock C. G. Antisera to neutrophils, lymph node cells, and thymus cells of the guinea pig: hematological effects and antibody localization. Transplantation. 1968 Jan;6(1):70–83. [PubMed] [Google Scholar]
  11. Loewi G., Temple A., Nind A. P., Axelrad M. A study of the effects of anti-macrophage sera. Immunology. 1969 Jan;16(1):99–106. [PMC free article] [PubMed] [Google Scholar]
  12. Lubaroff D. M., Waksman B. H. Bone marrow as a source of cells in reactions of cellular hypersensitivity. I. Passive transfer of tuberculin sensitivity in syngeneic systems. J Exp Med. 1968 Dec 1;128(6):1425–1435. doi: 10.1084/jem.128.6.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Maclaurin B. P., Humm J. A. Macrophage specificity of antiserum against thymus lymphocytes. Clin Exp Immunol. 1970 Jan;6(1):125–136. [PMC free article] [PubMed] [Google Scholar]
  14. Martin W. J., Miller J. F. Cell to cell interaction in the immune response. IV. Site of action of antilymphocyte globulin. J Exp Med. 1968 Oct 1;128(4):855–874. doi: 10.1084/jem.128.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. PEARSON C. M., WOOD F. D. PASSIVE TRANSFER OF ADJUVANT ARTHRITIS BY LYMPH NODE OR SPLEEN CELLS. J Exp Med. 1964 Oct 1;120:547–560. doi: 10.1084/jem.120.4.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Panijel J., Cayeux P. Immunosuppressive effects of macrophage antiserum. Immunology. 1968 Jun;14(6):769–780. [PMC free article] [PubMed] [Google Scholar]
  17. Putnam D. A., Lubaroff D. M., Waksman B. H. Bone marrow as source of cells in reactions of cellular hypersensitivity. 3. Adjuvant arthritis in the rat. Arthritis Rheum. 1969 Jun;12(3):215–219. doi: 10.1002/art.1780120308. [DOI] [PubMed] [Google Scholar]
  18. SEVER J. L. Application of a microtechnique to viral serological investigations. J Immunol. 1962 Mar;88:320–329. [PubMed] [Google Scholar]
  19. Turk J. L., Willoughby D. A., Stevens J. E. An analysis of the effects of some types of anti-lymphocyte sera on contact hypersensitivity and certain models of inflammation. Immunology. 1968 May;14(5):683–695. [PMC free article] [PubMed] [Google Scholar]
  20. Unanue E. R., Cerottini J. C. The function of macrophages in the immune response. Semin Hematol. 1970 Apr;7(2):225–248. [PubMed] [Google Scholar]
  21. Unanue E. R. Properties and some uses of anti-macrophage antibodies. Nature. 1968 Apr 6;218(5136):36–38. doi: 10.1038/218036a0. [DOI] [PubMed] [Google Scholar]
  22. Valentine M. D., Bloch K. J., Austen K. F. Mechanisms of immunologic injury of rat peritoneal mast cells. 3. Cytotoxic histamine release. J Immunol. 1967 Jul;99(1):98–110. [PubMed] [Google Scholar]
  23. WAKSMAN B. H., ARBOUYS S., ARNASON B. G. The use of specific "lymphocyte" antisera to inhibit hypersensitive reactions of the "delayed" type. J Exp Med. 1961 Dec 1;114:997–1022. doi: 10.1084/jem.114.6.997. [DOI] [PMC free article] [PubMed] [Google Scholar]

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