Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1978 Feb;90(2):497–520.

Suggested models of ecotaxopathy in lymphoreticular malignancy. A role for iron-binding proteins in the control of lymphoid cell migration.

M de Sousa, A Smithyman, C Tan
PMCID: PMC2018158  PMID: 304676

Abstract

In the present paper we apply the "ecotaxis hypothesis" to the analysis of lymphocyte distribution in Hodgkin's disease and other forms of lymphoid malignancy. The results lead us to consider the possiblity that metal-binding proteins, namely ferritin, transferrin and lactoferrin, play a role in lymphocyte ecotaxopahty. It is suggested that in Hodgkin's disease, a failure of lymph node and spleen monocytes to handle iron normally could explain most of the hematologic, immunologic, pathologic, and epidemiologic features of the disease.

Full text

PDF
497

Images in this article

520Figure 5
on p.520
520Figure 6
on p.520
517Figure 1
on p.517
517Figure 2
on p.517
518Figure 3
on p.518
519Figure 4
on p.519

Selected References

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

  1. Beamish M. R., Jones P. A., Trevett D., Evans I. H., Jacobs A. Iron metabolism in Hodgkin's disease. Br J Cancer. 1972 Dec;26(6):444–452. doi: 10.1038/bjc.1972.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bieber C. P., Bieber M. M. Detection of ferritin as a circulating tumor-associated antigen in Hodgkin's disease. Natl Cancer Inst Monogr. 1973 May;36:147–157. [PubMed] [Google Scholar]
  3. Case D. C., Jr, Hansen J. A., Corrales E., Young C. W., Dupont B., Pinsky C. M., Good R. A. Depressed in vitro lymphocyte responses to PHA in patients with Hodgkin disease in continuous long remissions. Blood. 1977 May;49(5):771–778. [PubMed] [Google Scholar]
  4. Cripps D. J., Hawgood R. S., Magnus I. A. Iodine tungsten fluorescence microscopy for porphyrin fluorescence. A study on erythropoietic protoporphyria. Arch Dermatol. 1966 Jan;93(1):129–137. [PubMed] [Google Scholar]
  5. Doerken H. Letter: Familial Hodgkin's disease. Lancet. 1974 Dec 14;2(7894):1463–1463. doi: 10.1016/s0140-6736(74)90134-2. [DOI] [PubMed] [Google Scholar]
  6. Dumont A. E., Ford R. J., Becker F. F. Siderosis of lymph nodes patients with Hodgkin's disease. Cancer. 1976 Sep;38(3):1247–1252. doi: 10.1002/1097-0142(197609)38:3<1247::aid-cncr2820380326>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  7. Eshhar Z., Order S. E., Katz D. H. Ferritin, a Hodgkin's disease associated antigen. Proc Natl Acad Sci U S A. 1974 Oct;71(10):3956–3960. doi: 10.1073/pnas.71.10.3956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Evans A. R., Hancock B. W., Brown M. J., Richmond J. A small cluster of Hodgkin's disease. Br Med J. 1977 Apr 23;1(6068):1056–1057. doi: 10.1136/bmj.1.6068.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ford W. L. Lymphocyte migration and immune responses. Prog Allergy. 1975;19:1–59. doi: 10.1159/000313381. [DOI] [PubMed] [Google Scholar]
  10. Freitas A. A., De Sousa M. Control mechanism of lymphocyte traffic. A study of the action of two sulfated polysaccharides on the distribution of 51Cr- and [3H]adenosine-labeled mouse lymph node cells. Cell Immunol. 1977 Jun 1;31(1):62–76. doi: 10.1016/0008-8749(77)90007-7. [DOI] [PubMed] [Google Scholar]
  11. Freitas A. A., de Sousa M. Control mechanism of lymphocyte traffic. Altered migration of 51Cr-labeled mouse lymph node cells pretreated in vitro with phospholipases. Eur J Immunol. 1976 Oct;6(10):703–711. doi: 10.1002/eji.1830061009. [DOI] [PubMed] [Google Scholar]
  12. Freitas A. A., de Sousa M. The role of cell interactions in the control of lymphocyte traffic. Cell Immunol. 1976 Mar 15;22(2):345–350. doi: 10.1016/0008-8749(76)90035-6. [DOI] [PubMed] [Google Scholar]
  13. GESNER B. M., GINSBURG V. EFFECT OF GLYCOSIDASES ON THE FATE OF TRANSFUSED LYMPHOCYTES. Proc Natl Acad Sci U S A. 1964 Sep;52:750–755. doi: 10.1073/pnas.52.3.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goos M., Kaiserling E., Lennert K. Mycosis fungoides: model for T-lymphocyte homing to the skin? Br J Dermatol. 1976 Feb;94(2):221–222. doi: 10.1111/j.1365-2133.1976.tb04374.x. [DOI] [PubMed] [Google Scholar]
  15. HADDOW A., HORNING E. S. On the carcinogenicity of an iron-dextran complex. J Natl Cancer Inst. 1960 Jan;24:109–147. [PubMed] [Google Scholar]
  16. Henry L. "Accidental" involution of the human thymus. J Pathol Bacteriol. 1968 Oct;96(2):337–343. doi: 10.1002/path.1700960211. [DOI] [PubMed] [Google Scholar]
  17. Hirshaut Y., Reagan R. L., Perry S., De Vita V., Jr, Barile M. F. The search for a viral agent in Hodgkin's disease. Cancer. 1974 Oct;34(4):1080–1089. doi: 10.1002/1097-0142(197410)34:4<1080::aid-cncr2820340418>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  18. Hyman G. A., Sommers S. C. The development of Hodgkin's disease and lymphoma during anticonvulsant therapy. Blood. 1966 Sep;28(3):416–427. [PubMed] [Google Scholar]
  19. JANDL J. H., KATZ J. H. The plasma-to-cell cycle of transferrin. J Clin Invest. 1963 Mar;42:314–326. doi: 10.1172/JCI104718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jaffe N., Bishop J. M. The serum iron level, hematocrit, sedimentation rate, and leukocyte alkaline phosphatase level in pediatric patients with Hodgkin's disease. Cancer. 1970 Aug;26(2):332–337. doi: 10.1002/1097-0142(197008)26:2<332::aid-cncr2820260214>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  21. Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jones P. A., Miller F. M., Worwood M., Jacobs A. Ferritinaemia in leukaemia and Hodgkin's disease. Br J Cancer. 1973 Mar;27(3):212–217. doi: 10.1038/bjc.1973.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kaplan H. S. Hodgkin's disease and other human malignant lymphomas: advances and prospects--G.H.A. Clowes Memorial Lecture. Cancer Res. 1976 Nov;36(11 Pt 1):3863–3878. [PubMed] [Google Scholar]
  24. Kaur J., Catovsky D., Spiers A. S., Galton D. A. Increase of T lymphocytes in the spleen in chronic granulocytic leukaemia. Lancet. 1974 May 4;1(7862):834–836. doi: 10.1016/s0140-6736(74)90484-x. [DOI] [PubMed] [Google Scholar]
  25. Lavender J. P., Lowe J., Barker J. R., Burn J. I., Chaudhri M. A. Gallium 67 citrate scanning in neoplastic and inflammatory lesions. Br J Radiol. 1971 May;44(521):361–366. doi: 10.1259/0007-1285-44-521-361. [DOI] [PubMed] [Google Scholar]
  26. Linder M. C., Munro H. N. Metabolic and chemical features of ferritins, a series of iron-inducible tissue proteins. Am J Pathol. 1973 Aug;72(2):263–282. [PMC free article] [PubMed] [Google Scholar]
  27. Long J. C., Zamecnik P. C., Aisenberg A. C., Atkins L. Tissue culture studies in Hodgkin's disease: Morphologic, cytogenetic, cell surface, and enzymatic properties of cultures derived from splenic tumors. J Exp Med. 1977 Jun 1;145(6):1484–1500. doi: 10.1084/jem.145.6.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lukes R. J., Butler J. J. The pathology and nomenclature of Hodgkin's disease. Cancer Res. 1966 Jun;26(6):1063–1083. [PubMed] [Google Scholar]
  29. Masson P. L., Heremans J. F., Schonne E. Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med. 1969 Sep 1;130(3):643–658. doi: 10.1084/jem.130.3.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matchett K. M., Huang A. T., Kremer W. B. Impaired lymphocyte transformation in Hodgkin's disease. Evidence for depletion of circulating t-lymphocytes. J Clin Invest. 1973 Aug;52(8):1908–1917. doi: 10.1172/JCI107374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ohkuma S., Noguchi H., Amano F., Mizuno D., Yasuda T. Synthesis of apoferritin in mouse peritoneal macrophages. Characterization of 20 S particles. J Biochem. 1976 Jun;79(6):1365–1376. doi: 10.1093/oxfordjournals.jbchem.a131191. [DOI] [PubMed] [Google Scholar]
  32. Parrott D. M., De Sousa M. Thymus-dependent and thymus-independent populations: origin, migratory patterns and lifespan. Clin Exp Immunol. 1971 May;8(5):663–684. [PMC free article] [PubMed] [Google Scholar]
  33. Payne S. V., Jones D. B., Haegert D. G., Smith J. L., Wright D. H. T and B lymphocytes and Reed-Sternberg cells in Hodgkin's disease lymph nodes and spleens. Clin Exp Immunol. 1976 May;24(2):280–286. [PMC free article] [PubMed] [Google Scholar]
  34. Phillips J. L., Azari P. Zinc transferrin. Enhancement of nucleic acid synthesis in phytohemagglutinin-stimulated human lymphocytes. Cell Immunol. 1974 Jan;10(1):31–37. doi: 10.1016/0008-8749(74)90148-8. [DOI] [PubMed] [Google Scholar]
  35. Phillips J. L. Specific binding of zinc transferrin to human lymphocytes. Biochem Biophys Res Commun. 1976 Sep 20;72(2):634–639. doi: 10.1016/s0006-291x(76)80087-3. [DOI] [PubMed] [Google Scholar]
  36. Robbins E., Pederson T. Iron: its intracellular localization and possible role in cell division. Proc Natl Acad Sci U S A. 1970 Aug;66(4):1244–1251. doi: 10.1073/pnas.66.4.1244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Robertson A. G., Dick W. C. Intramuscular iron and local oncogenesis. Br Med J. 1977 Apr 9;1(6066):946–946. doi: 10.1136/bmj.1.6066.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rudland P. S., Durbin H., Clingan D., de Asua L. J. Iron salts and transferrin are specifically required for cell division of cultured 3T6 cells. Biochem Biophys Res Commun. 1977 Apr 11;75(3):556–562. doi: 10.1016/0006-291x(77)91508-x. [DOI] [PubMed] [Google Scholar]
  39. SCHIER W. W., ROTH A., OSTROFF G., SCHRIFT M. H. Hodgkin's disease and immunity. Am J Med. 1956 Jan;20(1):94–99. doi: 10.1016/0002-9343(56)90176-0. [DOI] [PubMed] [Google Scholar]
  40. Sainte-Marie G. The autofluorescent cells of the rat thymus under certain experimental conditions. Proc Soc Exp Biol Med. 1966 Jul;122(3):696–700. doi: 10.3181/00379727-122-31230. [DOI] [PubMed] [Google Scholar]
  41. Sausville E. A., Peisach J., Horwitz S. B. A role for ferrous ion and oxygen in the degradation of DNA by bleomycin. Biochem Biophys Res Commun. 1976 Dec 6;73(3):814–822. doi: 10.1016/0006-291x(76)90882-2. [DOI] [PubMed] [Google Scholar]
  42. Sheagren J. N., Block J. B., Wolff S. M. Reticuloendothelial system phagocytic function in patients with Hodgkin's disease. J Clin Invest. 1967 May;46(5):855–862. doi: 10.1172/JCI105585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Soltys H. D., Brody J. I. Synthesis of transferrin by human peripheral blood lymphocytes. J Lab Clin Med. 1970 Feb;75(2):250–257. [PubMed] [Google Scholar]
  44. Sousa M. D., Yang M., Lopes-Corrales E., Tan C., Hansen J. A., Dupont B., Good R. A. Ecotaxis: the principle and its application to the study of Hodgkin's disease. Clin Exp Immunol. 1977 Jan;27(1):143–151. [PMC free article] [PubMed] [Google Scholar]
  45. Stamper H. B., Jr, Woodruff J. J. An in vitro model of lymphocyte homing. I. Characterization of the interaction between thoracic duct lymphocytes and specialized high-endothelial venules of lymph nodes. J Immunol. 1977 Aug;119(2):772–780. [PubMed] [Google Scholar]
  46. Steigbigel R. T., Lambert L. H., Jr, Remington J. S. Polymorphonuclear leukocyte, monocyte, and macrophage bactericidal function in patients with Hodgkin's disease. J Lab Clin Med. 1976 Jul;88(1):54–62. [PubMed] [Google Scholar]
  47. Van Snick J. L., Masson P. L., Heremans J. F. The involvement of lactoferrin in the hyposideremia of acute inflammation. J Exp Med. 1974 Oct 1;140(4):1068–1084. doi: 10.1084/jem.140.4.1068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Van Snick J. L., Masson P. L. The binding of human lactoferrin to mouse peritoneal cells. J Exp Med. 1976 Dec 1;144(6):1568–1580. doi: 10.1084/jem.144.6.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Vianna N. J., Davies J. N., Polan A. K., Wolfgang P. Familial Hodgkin's disease: an environmental and genetic disorder. Lancet. 1974 Oct 12;2(7885):854–857. doi: 10.1016/s0140-6736(74)91198-2. [DOI] [PubMed] [Google Scholar]
  50. Vianna N. J., Greenwald P., Davies J. N. Tonsillectomy and Hodgkin's disease: the lymphoid tissue barrier. Lancet. 1971 Feb 27;1(7696):431–432. doi: 10.1016/s0140-6736(71)92416-0. [DOI] [PubMed] [Google Scholar]
  51. Weinberg E. D. Iron and susceptibility to infectious disease. Science. 1974 May 31;184(4140):952–956. doi: 10.1126/science.184.4140.952. [DOI] [PubMed] [Google Scholar]
  52. Woodruff J. J., Gesner B. M. The effect of neuraminidase on the fate of transfused lymphocytes. J Exp Med. 1969 Mar 1;129(3):551–567. doi: 10.1084/jem.129.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Woodruff J. J. Role of lymphocyte surface determinants in lymph node homing. Cell Immunol. 1974 Sep;13(3):378–384. doi: 10.1016/0008-8749(74)90257-3. [DOI] [PubMed] [Google Scholar]
  54. Woodruff J., Gesner B. M. Lymphocytes: circulation altered by trypsin. Science. 1968 Jul 12;161(3837):176–178. doi: 10.1126/science.161.3837.176. [DOI] [PubMed] [Google Scholar]
  55. Young R. C., Corder M. P., Haynes H. A., DeVita V. T. Delayed hypersensitivity in Hodgkin's disease. A study of 103 untreated patients. Am J Med. 1972 Jan;52(1):63–72. doi: 10.1016/0002-9343(72)90008-3. [DOI] [PubMed] [Google Scholar]
  56. ZAMENHOF S., GRIBOFF G., MARULLO N. Studies on the resistance of desoxyribonucleic acids to physical and chemical factors. Biochim Biophys Acta. 1954 Apr;13(4):459–470. doi: 10.1016/0006-3002(54)90362-5. [DOI] [PubMed] [Google Scholar]
  57. van Snick J. L., Markowetz B., Masson P. L. The ingestion and digestion of human lactoferrin by mouse peritoneal macrophages and the transfer of its iron into ferritin. J Exp Med. 1977 Sep 1;146(3):817–827. doi: 10.1084/jem.146.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES