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The biochemistry of lymphocyte-derived mediators of immunological inflammation

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Abstract

Evidence is presented to indicate that there exists in lymphoid tissue, as a result of transforming lymphocytes, a new lymphokine which is chemotactically specific for lymphocytes, called ‘lymphotactin’. Lymphotactin has been purified to electrophoretic homogeneity; has a molecular weight of 10,500 D and an isoelectric point of 5.9. Its role in amplifying the immune defense system by recruitment of naive lymphocytes into propinquity with the challenging antigen is suggested.

Purification of macrophage migration inhibitory factor from thymus extracts to electrophoretic homogeneity leads to a compound of molecular weight of 36,500 D and an IEP of 6.9. Chemically it contains sialic acid ando-methyl glucopyranoside as its only carbohydrates. Purified MIF activates the macrophage phagocytically.

Skin reactive factor and lymph node permeability factor have been isolated and purified and are found to be inhibited by pepstatin and antihistamine and to have an isoelectric point of pH 4.2 and a molecular weight of 50,000–100,000 D. It is believed that this anionic permeability increasing agent actually arises from the lysosomes of macrophages and lymphoblasts (the normal small lymphocyte having essentially no lysosomal organelles). The mononuclear cell infiltration characteristic of crude SRF and LNPF may proceed from their being contaminated with lymphotactin.

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References

  1. P. Ward, H.G. Remold andJ.R. David,The Production by Antigen-Stimulated Lymphocytes of Leucotactic Factor Distinct from Migration Inhibitory Factor, Cell. Immunol.2, 162–174 (1970).

    Google Scholar 

  2. R.T. McCluskey, B. Benacerraf andJ.W. McCluskey,Studies on the Specificity of the Cellular Infiltrate in Delayed Hypersensitivity Reactions, J. Immunol.90, 466–477 (1963).

    Google Scholar 

  3. P.A. Ward, C.R. Offen andJ.R. Montgomery,Chemoattractants of Leucocytes with Special Reference to Lymphocytes, Fed. Proc.30, 1721–1724 (1971).

    Google Scholar 

  4. J.C. Houck andC.M. Chang,Properties of Lymphocyte Chemotactic Factor (Lymphotactin) in Thymus, Inflammation1, 217–221 (1976).

    Google Scholar 

  5. E. Zipilvan, B. Hudson andW. Blatt,Separation of Immunologically Active Fragments by Membrane Partition Chromatography, Anal. Biochem.30, 91–98 (1969).

    Google Scholar 

  6. B.R. Bloom andB. Bennett,Mechanism of a Reaction in vitro Associated with Delayed-Type Hypersensitivity, Science153, 80–82 (1966).

    Google Scholar 

  7. J.R. David,Delayed Hypersensitivity in vitro: Its Mediation by Cell Free Substances Formed by Lymphoid Cell-Antigen Interaction, Proc. Nat. Acad. Sci.56, 72–77 (1966).

    Google Scholar 

  8. A.R. Rich andM.R. Lewis,The Nature of Allergy in Tuberculosis as Revealed by Tissue Culture Studies, Bull. Johns Hopkins Hosp.50, 115–131 (1932).

    Google Scholar 

  9. M. George andJ.H. Vaughn,In vitro Cell Migration as a Model for Delayed Sensitivity, Proc. Soc. Exp. Biol. Med.111, 514–521 (1962).

    Google Scholar 

  10. J.R. David, S. Al-Askari, H.S. Lawrence andL. Thomas,Delayed Hypersensitivity in vitro. I. The Specificity of Inhibition of Cell Migration by Antigens, J. Immuno.93, 264–273 (1964).

    Google Scholar 

  11. J.R. David, H.S. Lawrence andL. Thomas,Delayed Hypersensitivity in vitro. II. Effect of Sensitive Cells on Normal Cells in the Presence of Antigen, J. Immunol.93, 274–278 (1964).

    Google Scholar 

  12. J.R. David andS.T. Schlossmann,Immunochemical Studies on the Specificity of Cellular Hypersensitivity. The in vitro Inhibition of Peritoneal Exudate Cell Migration by Chemically Defined Antigens, J. Exp. Med.128, 1451–1459 (1968).

    Google Scholar 

  13. J.C. Houck andC.M. Chang,A New Sensitive Assay for Macrophage Inhibitory Factor, Proc. Soc. Exp. Biol. Med.142, 800–803 (1973).

    Google Scholar 

  14. G.A. Granger, G.E. Moore, J.G. White et al.,Production of Lymphotoxin and Migration Inhibitory Factor by Established Human Lymphocytic Cell Lines, J. Immunol.104, 1476–1485 (1970).

    Google Scholar 

  15. J.E. Clausen,Migration Inhibitory Effect of Cell-Free Supernatants from Mixed Human Lymphocyte Cultures, J. Immunol.108, 453–459 (1972).

    Google Scholar 

  16. J.B. Hay, P.J. Lachmann andZ. Trnka,The Appearance of Migration Inhibition Factor and a Mitogen in Lymph Draining Tuberculin Reactions, Eur. J. Immunol.3, 127–131 (1973).

    Google Scholar 

  17. D.E. McFarlin andB. Balfour,Contact Sensitivity in the Pig, Immunology25, 995–1009 (1973).

    Google Scholar 

  18. B. Bennett andB. Bloom,Reaction in vivo and in vitro Produced by a Soluble Substance Associated with Delayed-Type Hypersensitivity, Proc. Nat. Acad. Sci. USA59, 756–762 (1968).

    Google Scholar 

  19. D.C. Dumonde, D.A. Page, M. Matthew andR.A. Wolstencroft,Role of Lymphocyte Activation Products (LAP) in Cell-Mediated Immunity. I. Preparation of Partial Purification of Guinea Pig LAP, Clin. Exp. Immunol.10, 25–47 (1972).

    Google Scholar 

  20. H.G. Remold andJ.R. David,Further Studies in MIF: Evidence for its Glycoprotein Nature, J. Immunol.107, 1090–1098 (1971).

    Google Scholar 

  21. H.G. Remold, A.B. Katz, E. Haber andJ.R. David,Studies on Migration Inhibitory Factor (MIF): Recovery of MIF Activity after Purification by Gel Filtration and Disc Electrophoresis, Cell. Immunol.1, 133–145 (1970).

    Google Scholar 

  22. H.G. Remold, R.A. David andJ.R. David,Characterization of Migration Inhibitory Factor (MIF) from Guinea Pig Lymphocytes Stimulated with Concanavalin A, J. Immunol.109, 578–586 (1972).

    Google Scholar 

  23. H.G. Remold,Requirement for α-l-Fucose on the Macrophage Membrane Receptor for MIF, J. Exp. Med.138, 1065–1076 (1973).

    Google Scholar 

  24. R.A. Fox, D.S. Gregory andJ.D. Feldman,Macrophage Receptors for Migration Inhibitory Factor (MIF), Migration Stimulatory Factor (MSF), and Agglutinating Factor, J. Immunol.112, 1867–1872 (1974).

    Google Scholar 

  25. J.C. Houck, C.M. Chang andM. Platt,Macrophage Migration Inhibitory Factor in Thymus, Proc. Soc. Exp. Biol. Med.143, 858–861 (1973).

    Google Scholar 

  26. J.C. Houck andC.M. Chang,Purification of Thymic Macrophage Migration Inhibitory Factor (MIF), Inflammation2, 189–201 (1976).

    Google Scholar 

  27. J.C. Houck, unpublished observations.

  28. J.R. David,Macrophage Migration, Fed Proc.27, 6 (1968).

    Google Scholar 

  29. K. Havemann, M. Horvat, C.P. Sodomann et al.,Protease Activity as a Possible Mechanism of Migration Inhibitory Factor, Immunology2, 97–99 (1972).

    Google Scholar 

  30. H.G. Remold,The Enhancement of MIF Activity by Inhibition of Macrophage Associated Esterases, J. Immunol.112, 1571–1577 (1974).

    Google Scholar 

  31. J. Marks andD.M. James,The Effect of Tuberculin on Sensitized and Normal Leucocytes, J. Hyg. (Camb.)51, 340–346 (1953).

    Google Scholar 

  32. D.A. Willoughby, B. Boughton andH.O. Schild,A Factor Capable of Increasing Vascular Permeability Present in Lymph Node Cells, Immunology6, 484–498 (1963).

    Google Scholar 

  33. D.A. Willoughby, M. Walters andW. Spector,Lymph Node Permeability Factor in the DNP Skin Hypersensitivity Reaction in Guinea Pig, Immunology8, 578–584 (1965).

    Google Scholar 

  34. A. Lykke, D.A. Willoughby andE. Koshe,Thymic Permeability Factor: Its Relationship to Lymph-Node Permeability Factor and its Antagonism and Other Anti-Inflammatory Agents, J. Path. Bact.94, 381–388 (1967).

    Google Scholar 

  35. E. Pick, J. Krejci andJ. Turk,Interaction Between ‘Sensitized Lymphocytes’ and Antigen in vitro: (1) The Release of Skin Reactive Factor, Immunology17, 741–767 (1969).

    Google Scholar 

  36. E. Pick, J. Krejci andJ. Turk,In vitro Production and Assessment of Activity of Skin Reactive Factors Released by Lymphoid Cells and Associated with Cellular Immunity, in:In Vitro Methods in Cell-Mediated Immunity (Eds. B. Bloom and P. Glade; Academic Press, New York; 1971), pp. 515–530.

    Google Scholar 

  37. J. Judah andD.A. Willoughby,A Quantitative Method for the Study of Capillary Permeability: Extraction and Determination of Trypan Blue in Tissues, J. Path. Bact.83, 567–572 (1962).

    Google Scholar 

  38. J.C. Houck, D. Barrantes andH. Irausquin,Skin Reactive Factor and Lymph Node Permeability Factor, Agents and Actions3, 278–283 (1973).

    Google Scholar 

  39. N.N. Aronson andE.A. Davidson,Lysosomal Hyaluronidase from Rat Liver, J. Biol. Chem.242, 437–440 (1967).

    Google Scholar 

  40. J. Ferguson, J. Andrews, I. Voynick andJ. Fruton,The Specificity of Cathepsin D, J. Biol. Chem.248, 6701–6708 (1973).

    Google Scholar 

  41. M. Greenbaum,Leucocyte Kininogenases and Leukokinins from Normal and Malignant Cells, Amer. J. Pathol.68, 613–623 (1972).

    Google Scholar 

  42. N.S. Ranadive andC.S. Cochrane,Mechanism of Histamine Release from Mast Cells by Cationic Protein (Band 2) from Neutrophil Lysosomes, J. Immunol.106, 506–516 (1971).

    Google Scholar 

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Houck, J.C., Hellman, K.B. & Chang, C.M. The biochemistry of lymphocyte-derived mediators of immunological inflammation. Agents and Actions 8, 73–79 (1978). https://doi.org/10.1007/BF01972405

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