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.
Similar content being viewed by others
References
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).
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).
P.A. Ward, C.R. Offen andJ.R. Montgomery,Chemoattractants of Leucocytes with Special Reference to Lymphocytes, Fed. Proc.30, 1721–1724 (1971).
J.C. Houck andC.M. Chang,Properties of Lymphocyte Chemotactic Factor (Lymphotactin) in Thymus, Inflammation1, 217–221 (1976).
E. Zipilvan, B. Hudson andW. Blatt,Separation of Immunologically Active Fragments by Membrane Partition Chromatography, Anal. Biochem.30, 91–98 (1969).
B.R. Bloom andB. Bennett,Mechanism of a Reaction in vitro Associated with Delayed-Type Hypersensitivity, Science153, 80–82 (1966).
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).
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).
M. George andJ.H. Vaughn,In vitro Cell Migration as a Model for Delayed Sensitivity, Proc. Soc. Exp. Biol. Med.111, 514–521 (1962).
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).
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).
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).
J.C. Houck andC.M. Chang,A New Sensitive Assay for Macrophage Inhibitory Factor, Proc. Soc. Exp. Biol. Med.142, 800–803 (1973).
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).
J.E. Clausen,Migration Inhibitory Effect of Cell-Free Supernatants from Mixed Human Lymphocyte Cultures, J. Immunol.108, 453–459 (1972).
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).
D.E. McFarlin andB. Balfour,Contact Sensitivity in the Pig, Immunology25, 995–1009 (1973).
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).
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).
H.G. Remold andJ.R. David,Further Studies in MIF: Evidence for its Glycoprotein Nature, J. Immunol.107, 1090–1098 (1971).
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).
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).
H.G. Remold,Requirement for α-l-Fucose on the Macrophage Membrane Receptor for MIF, J. Exp. Med.138, 1065–1076 (1973).
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).
J.C. Houck, C.M. Chang andM. Platt,Macrophage Migration Inhibitory Factor in Thymus, Proc. Soc. Exp. Biol. Med.143, 858–861 (1973).
J.C. Houck andC.M. Chang,Purification of Thymic Macrophage Migration Inhibitory Factor (MIF), Inflammation2, 189–201 (1976).
J.C. Houck, unpublished observations.
J.R. David,Macrophage Migration, Fed Proc.27, 6 (1968).
K. Havemann, M. Horvat, C.P. Sodomann et al.,Protease Activity as a Possible Mechanism of Migration Inhibitory Factor, Immunology2, 97–99 (1972).
H.G. Remold,The Enhancement of MIF Activity by Inhibition of Macrophage Associated Esterases, J. Immunol.112, 1571–1577 (1974).
J. Marks andD.M. James,The Effect of Tuberculin on Sensitized and Normal Leucocytes, J. Hyg. (Camb.)51, 340–346 (1953).
D.A. Willoughby, B. Boughton andH.O. Schild,A Factor Capable of Increasing Vascular Permeability Present in Lymph Node Cells, Immunology6, 484–498 (1963).
D.A. Willoughby, M. Walters andW. Spector,Lymph Node Permeability Factor in the DNP Skin Hypersensitivity Reaction in Guinea Pig, Immunology8, 578–584 (1965).
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).
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).
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.
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).
J.C. Houck, D. Barrantes andH. Irausquin,Skin Reactive Factor and Lymph Node Permeability Factor, Agents and Actions3, 278–283 (1973).
N.N. Aronson andE.A. Davidson,Lysosomal Hyaluronidase from Rat Liver, J. Biol. Chem.242, 437–440 (1967).
J. Ferguson, J. Andrews, I. Voynick andJ. Fruton,The Specificity of Cathepsin D, J. Biol. Chem.248, 6701–6708 (1973).
M. Greenbaum,Leucocyte Kininogenases and Leukokinins from Normal and Malignant Cells, Amer. J. Pathol.68, 613–623 (1972).
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).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Issue Date:
DOI: https://doi.org/10.1007/BF01972405