Subcellular Morphology and Biochemistry of Eosinophils

  • A. M. Dvorak
  • S. J. Ackerman
  • P. F. Weller
Part of the Blood Cell Biochemistry book series (BLBI, volume 2)


The purpose of this chapter is to illustrate the power of ultrastructural morphologic analysis either alone or combined with newer ultrastructural protocols in aiding our understanding of eosinophil biology. We draw from our personal knowledge of eosinophils from several species (human, mouse, guinea pig, rat, rabbit, opossum, and monkey) but most particularly from our ultrastructural studies of human eosinophils in vivo and in vitro. We first review general substructural features of mature eosinophils as a granulocyte class and then review the established morphologic rules for eosinophil differentiation and maturation by emphasizing the morphology of eosinophilic myelocytes in general. Included in this discussion is an overview of eosinophil granulogenesis. We also consider some key sources of confusion regarding eosinophil morphology and address particular criteria needed to avoid these potential pitfalls.


Lipid Body Bullous Pemphigoid Human Basophil Human Eosinophil Tissue Eosinophil 


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  1. Ackerman, S. J., Loegering, D. A., and Gleich, G. J., 1980, The human eosinophil Charcot-Leyden crystal protein: Biochemical characteristics and measurement by radioimmunoassay, J. Immunol. 125: 2118–2126.PubMedGoogle Scholar
  2. Ackerman, S. J., Durack, D. T., and Gleich, G. J., 1982a, Eosinophil effector mechanisms in health and disease, in Advances in Host Defense Mechanisms, Vol. 1 ( J. I. Gallin and A. S. Fauci, eds.), pp. 269–293, Raven Press, New York.Google Scholar
  3. Ackerman, S. J., Weil, G. J., and Gleich, G. J., 1982b, Formation of Charcot-Leyden crystals by human basophils, J. Exp. Med. 155: 1597–1609.PubMedGoogle Scholar
  4. Ackerman, S. J., Kephart, G. M., Habermann, T. M., Greipp, P. R., and Gleich, G. J., 1983a, Localization of eosinophil granule major basic protein in human basophils, J. Exp. Med. 158: 946–961.PubMedGoogle Scholar
  5. Ackerman, S. J., Loegering, D. A., Venge, P., Olsson, I., Harley, J. B., Fauci, A. S., and Gleich, G. J., 1983b, Distinctive cationic proteins of the human eosinophil granule: Major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin, J. Immunol. 131: 2977–2982.PubMedGoogle Scholar
  6. Ackerman, S. J., Gleich, G. J., Loegering, D. A., Richardson, B. A., and Butterworth, A. E., 1985, Comparative toxicity of purified human eosinophil granule cationic proteins for schistosomula of Schistosoma mansoni, Am. J. Trop. Med. Hyg. 34: 735–745.PubMedGoogle Scholar
  7. Archer, T. G., and Blackwood, A., 1965, Formation of Charcot-Leyden crystals in human eosinophils and basophils and study of the composition of isolated crystals, J. Exp. Med. 122: 173–180.PubMedGoogle Scholar
  8. Ayres, W. W., and Starkey, N. M., 1950, Studies on Charcot-Leyden crystals, Blood 5: 254–266.PubMedGoogle Scholar
  9. Bainton, D. F., and Farquhar, M. G., 1966, Origin of granules in polymorphonuclear leukocytes. Two types derived from opposite faces of the Golgi complex in developing granulocytes, J. Cell Biol. 28: 277–301.PubMedGoogle Scholar
  10. Bainton, D. F., and Farquhar, M. G., 1968, Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. II. Cytochemistry and electron microscopy of bone marrow cells, J. Cell Biol. 39: 299–317.PubMedGoogle Scholar
  11. Bainton, D. F., and Farquhar, M. G., 1970, Segregation and packaging of granule enzymes in eosinophilic leukocytes, J. Cell Biol. 45: 54–73.PubMedGoogle Scholar
  12. Bass, D. A., Grover, W. H., Lewis, J. C., Szejda, P., DeChatelet, L. R., and McCall, C. E., 1980, Comparison of human eosinophils from normals and patients with eosinophilia, J. Clin. Invest. 66: 1265–1273.PubMedGoogle Scholar
  13. Bass, D. A., Phil, D., Lewis, J. C., Szejda, P., Cowley, L., and McCall, C. E., 1981, Activation of lysosomal acid phosphatase of eosinophil leukocytes, Lab. Invest. 44: 403–409.PubMedGoogle Scholar
  14. Beeson, P. B., and Bass, D. A., 1977, The eosinophil, in Major Problems in Internal Medicine, Vol. 14 ( L. H. Smith, ed.), pp. 39–42, W. B. Saunders Co., Philadelphia.Google Scholar
  15. Bessis, M., and Tabuis, J., 1955, Formation de crystaux à partir des leucocytes basophiles, C.R. Soc. Biol. 149: 873–875.Google Scholar
  16. Butterfield, J. H., Ackerman, S. J., Scott, R. E., Pierre, R. V., and Gleich, G. J., 1984, Evidence for the secretion of human eosinophil granule major basic protein and Charcot-Leyden crystal protein during eosinophil maturation, Exp. Hematol. 12: 163–170.PubMedGoogle Scholar
  17. Butterfield, J. H., Kephart, G. M., Banks, P. M., and Gleich, G. J., 1986, Extracellular deposition of eosinophil granule major basic protein in lymph nodes of patients with Hodgkin’s disease, Blood 68: 1250–1256.PubMedGoogle Scholar
  18. Butterworth, A. E., Wassom, D. L., Gleich, G. J., Loegering, D. A., and David, J. R., 1979, Damage to schistosomula of Schistosoma mansoni induced directly by eosinophil major basic protein, J. Immunol. 122: 221–229.PubMedGoogle Scholar
  19. Caulfield, J. P., Lenzi, H., Elsas, P., and Dessein, A. J., 1985, Ultrastructure of the attack of eosinophils stimulated by blood mononuclear cell products on schistosomula of Schistosoma monsoni, Am. J. Pathol. 120: 380–390.PubMedGoogle Scholar
  20. Charcot, J. M., and Robin, C., 1953, Observation de leucocythémie, C.R. Mem. Soc. Biol. 5: 44–50.Google Scholar
  21. Cotran, R. S., and Litt, M., 1969, The entry of granule-associated peroxidase into the phagocytic vacuoles of eosinophils, J. Exp. Med. 129: 1291–1306.PubMedGoogle Scholar
  22. Durack, D. T., Sumi, M., and Klebanoff, S. J., 1979, Neurotoxicity of human eosinophils, Proc. Natl. Acad. Sci. USA 76: 1443–1447.PubMedGoogle Scholar
  23. Durack, D. T., Ackerman, S. J., Loegering, D. A., and Gleich, G. J., 1981, Purification of human eosinophilderived neurotoxin, Proc. Natl. Acad. Sci. USA 8: 5165–5169.Google Scholar
  24. Dvorak, A. M., 1978, Biology and morphology of basophilic leukocytes, in Immediate Hypersensitivity: Modern Concepts and Developments, Vol. 7 ( M. K. Bach, ed.), pp. 369–405, Marcel Dekker, New York.Google Scholar
  25. Dvorak, A. M., 1980, Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: Cytotoxic potential in Crohn’s disease, J. Immunol. 125: 460–462.PubMedGoogle Scholar
  26. Dvorak, A. M., 1986a, Mast cell degranulation in human hearts, N. Engl. J. Med. 315: 969–970.PubMedGoogle Scholar
  27. Dvorak, A. M., 1986b, Morphologic expressions of maturation and function can affect the ability to identify mast cells and basophils in man, guinea pig and mouse, in Mast Cell Differentiation and Heterogeneity ( A. D. Befus, J. Bienenstock, and J. A. Denburg, eds.), pp. 95–114, Raven Press, New York.Google Scholar
  28. Dvorak, A. M., 1987, Monograph: Procedural guide to specimen handling for the diagnostic ultrastructural pathology service laboratory. J. Electron Microsc. Techn. 6: 255–301.Google Scholar
  29. Dvorak, A. M., 1988a, Ultrastructural pathology of Crohn’s disease, in Inflammatory Bowel Diseases—Basic Research and Clinical Applications ( H. Goebel’, B. M. Peskar, and M. Malchow, eds.), pp. 3–41, MTP Press, Ltd., Lancaster, England.Google Scholar
  30. Dvorak, A. M., 1988b, Morphologic and immunologic characterization of human basophils, 1879 to 1975, Riv. Immunol. Immunofarmacol. 8: 50–82.Google Scholar
  31. Dvorak, A. M., 1988e, The fine structure of human basophils and mast cells, in Mast Cells, Mediators and Disease ( S. T. Holgate, ed.), pp. 29–97, Kluwer Academic Publishers, Lancaster, England.Google Scholar
  32. Dvorak, A. M., 1989, Human mast cells, in Advances in Anatomy Embryology and Cell Biology, Vol. 114 ( F. Beck, W. Hild, W. Kriz, R. Ortmann, J. E. Pauly, and T. H. Schiebler, eds.), pp. 1–107, Springer-Verlag, Berlin.Google Scholar
  33. Dvorak, A. M., and Ackerman, S. J., 1989, Ultrastructural localization of the Charcot-Leyden crystal protein (lysophospholipase) to granules and intragranular crystals in mature human basophils, Lab. Invest. 60: 557–567.PubMedGoogle Scholar
  34. Dvorak, A. M., and Dickersin, G. R., 1979, Crohn’s disease, electron microscopic studies, in Pathology Annual–Part 2, Vol. 14 ( S. C. Sommers and P. P. Rosen, eds.), pp. 259–306, Appleton-Century-Crofts, New York.Google Scholar
  35. Dvorak, A. M., and Monahan, R. A., 1982, Crohn’s disease. Ultrastructural studies showing basophil leukocyte granule changes and lymphocyte parallel tubular arrays in peripheral blood, Arch. Pathol. Lab. Med. 106: 145–149.PubMedGoogle Scholar
  36. Dvorak, A. M., and Monahan, R. A., 1984, Chronic abdominal pain, malaise, constipation and diarrhea in a forty year old woman: Crohn’s disease, Norelco Rep. 31: 18–44.Google Scholar
  37. Dvorak, A. M., and Monahan, R. A., 1985, Guinea pig bone marrow basophilopoiesis, J. Exp. Pathol. 2: 1324.Google Scholar
  38. Dvorak, A. M., and Monahan-Earley, R. A., 1990, Ultrastructural Pathology. A Text-Atlas of Case Studies Illustrating the Correlative Clinical-Ultrastructural Pathologic Approach to Diagnosis, Verlag-Chemie Publishers, New York.Google Scholar
  39. Dvorak, A. M., and Silen, W., 1985, Differentiation between Crohn’s disease and other inflammatory conditions by electron microscopy, Ann. Surg. 201: 53–63.PubMedGoogle Scholar
  40. Dvorak, A. M., Dvorak, H. F., and Karnovsky, M. J., 1972, Uptake of horseradish peroxidase by guinea pig basophilic leukocytes, Lab. Invest. 26: 27–39.PubMedGoogle Scholar
  41. Dvorak, A. M., Mihm, M. C. Jr., and Dvorak, H. F., 1976, Degranulation of basophilic leukocytes in allergic contact dermatitis reactions in man, J. Immunol. 116: 687–695.PubMedGoogle Scholar
  42. Dvorak, A. M., Hammond, M. E., Morgan, E. S., and Dvorak, H. F., 1980a, Ultrastructural studies of macrophages: In vitro removal of cell coat with macrophage inhibition factor (MIF)-containing lymphocyte culture supernatants; chloroform extraction, phospholipase digestion and autoradiographic studies, J. Reticuloendothel. Soc. 27: 119–142.PubMedGoogle Scholar
  43. Dvorak, A. M., Hammond, M. E., Morgan, E., Orenstein, N. S., Galli, S. J., and Dvorak, H. F., 19806, Evidence for a vesicular transport mechanism in guinea pig basophilic leukocytes, Lab. Invest. 42: 263–276.Google Scholar
  44. Dvorak, A. M., Monahan, R. A., Osage, J. E., and Dickersin, G. R., 1980c, Crohn’s disease: Transmission electron microscopic studies. II. Immunologic inflammatory response. Alterations of mast cells, basophils, eosinophils, and the microvasculature, Hum. Pathol. 11: 606–619.PubMedGoogle Scholar
  45. Dvorak, A. M., Newball, H. H., Dvorak, H. F., and Lichtenstein, L. M., 1980d, Antigen-induced IgEmediated degranulation of human basophils, Lab. Invest. 43: 126–139.PubMedGoogle Scholar
  46. Dvorak, A. M., Osage, J. E., Monahan, R. A., and Dickersin, G. R., 1980e, Crohn’s disease: Transmission electron microscopic studies. III. Target tissues. Proliferation of and injury to smooth muscle and the autonomic nervous system, Hum. Pathol. 11: 620–634.PubMedGoogle Scholar
  47. Dvorak, A. M., Lett-Brown, M., Thueson, D., and Grant, J. A., 1981a, Complement-induced degranulation of human basophils, J. Immunol. 126: 523–528.PubMedGoogle Scholar
  48. Dvorak, A. M., Monahan, R. A., and Dickersin, G. R., 1981b, Diagnostic electron microscopy. I. Hematology: Differential diagnosis of acute lymphoblastic and acute myeloblastic leukemia. Use of ultrastructural peroxidase cytochemistry and routine electron microscopic technology, in Pathology Annual—Part I ( S. C. Sommers and P. P. Rosen, eds.), pp. 101–137, Appleton-Century-Crofts, New York.Google Scholar
  49. Dvorak, A. M., Mihm, M. C. Jr., Osage, J. E., Kwan, T. H., Austen, K. F., and Wintroub, B. U., 1982a, Bullous pemphigoid, an ultrastructural study of the inflammatory response: Eosinophil, basophil and mast cell granule changes in multiple biopsies from one patient, J. Invest. Dermatol. 78: 91–101.PubMedGoogle Scholar
  50. Dvorak, A. M., Nabel, G., Pyne, K., Cantor, H., Dvorak, H. F., and Galli, S. J., 1982b, Ultrastructural identification of the mouse basophil, Blood 59: 1279–1285.PubMedGoogle Scholar
  51. Dvorak, A. M., Dvorak, H. F., Peters, S. P., Schulman, E. S., MacGlashan, Jr., D. W., Pyne, K., Harvey, V. S., Galli, S. J., and Lichtenstein, L. M., 1983, Lipid bodies: Cytoplasmic organelles important to arachidonate metabolism in macrophages and mast cells, J. Immunol. 131: 2965–2976PubMedGoogle Scholar
  52. Dvorak, A. M., Dvorak, H. F., Peters, S. P., Schulman, E. S., MacGlashan, Jr., D. W., Pyne, K., Harvey, V. S., Galli, S. J., and Lichtenstein, L. M., Republished in J. Immunol. 132: 1586–1597, 1984.Google Scholar
  53. Dvorak, A. M., Hammel, I., Schulman, E. S., Peters, S. P., MacGlashan, Jr. D. W., Schleimer, R. P., Newball, H. H., Pyne, K., Dvorak, H. F., Lichtenstein, L. M., and Galli, S. J., 1984a, Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation, J. Cell Biol. 99: 1678–1687.PubMedGoogle Scholar
  54. Dvorak, A. M., Lett-Brown, M. A., Thueson, D. O., Pyne, K., Raghuprasad, P K., Galli, S. J., and Grant, J. A., 1984b, Histamine-releasing activity (HRA). III. HRA induces human basophil histamine release by provoking noncytotoxic granule exocytosis, Clin. Immunol. Immunopathol. 32: 142–150.PubMedGoogle Scholar
  55. Dvorak, A. M., Ishizaka, T., and Galli, S. J., 1985a, Ultrastructure of human basophils developing in vitro. Evidence for the acquisition of peroxidase by basophils and for different effects of human and murine growth factors on human basophil and eosinophil maturation, Lab. Invest. 53: 57–71.PubMedGoogle Scholar
  56. Dvorak, A. M., Klebanoff, S. J., Henderson, W. R., Monahan, R. A., Pyne, K., and Galli, S. J., 1985b, Vesicular uptake of eosinophil peroxidase by guinea pig basophils and by cloned mouse mast cells and granule-containing lymphoid cells, Am. J. Pathol. 118: 425–438.PubMedGoogle Scholar
  57. Dvorak, A. M., Schulman, E. S., Peters, S. P., MacGlashan, Jr., D. W., Newball, H. H., Schleimer, R. P., and Lichtenstein, L. M., 1985c, Immunoglobulin E-mediated degranulation of isolated human lung mast cells, Lab. Invest. 53: 45–56.PubMedGoogle Scholar
  58. Dvorak, A. M., Letourneau, L. Login, G. R., Weller, P. F., and Ackerman, S. J., 1988, Ultrastructural localization of the Charcot-Leyden crystal protein (lysophospholipase) to a distinct crystalloid-free granule population in mature human eosinophils, Blood 72: 150–158.PubMedGoogle Scholar
  59. Dvorak, A. M., Monahan-Earley, R. A., Estrella, P., Kissell, S., and Donahue, R. E., 1989a, Ultrastructure of monkey peripheral blood basophils stimulated to develop in vivo by recombinant human interleukin 3. Lab. Invest. 61: 677–690.PubMedGoogle Scholar
  60. Dvorak, A. M., Saito, H., Estrella, P., Kissell, S., Arai, N., and Ishizaka, T., 1989b, Ultrastucture of eosinophils and basophils stimulated to develop in human cord blood mononuclear cell cultures containing recombinant human interleukin-5 or interleukin-3, Lab. Invest. 61: 116–132.PubMedGoogle Scholar
  61. Dvorak, A. M., Weller, P. F., Monahan-Earley, R. A., Letourneau, L., and Ackerman, S. J., 1990, Ultrastructural localization of Charcot-Leyden crystal protein (lysophospholipase) and peroxidase in macrophages, eosinophils, and extracellular matrix of the hypereosinophilic syndrome in the skin, Lab. Invest. (in press).Google Scholar
  62. Egeston, A., Alumets, J., Mecklenburg, C. V., Palmegren, M., and Olsson, I., 1986, Localization of eosinophil cationic protein, major basic protein, and eosinophil peroxidase in human eosinophils by immunoelectron microscopic technique, J. Histochem. Cytochem. 34: 1399–1403.Google Scholar
  63. El-Hashimi, W., 1971, Charcot-Leyden crystals. Formation from primate and lack of formation from non-primate eosinophils, Am. J. Pathol. 65: 311–324.PubMedGoogle Scholar
  64. Fedorko, M., 1968, Formation of cytoplasmic granules in human eosinophilic myelocytes: An electron microscope autoradiographic study, Blood 31: 188–194.PubMedGoogle Scholar
  65. Filley, W. V., Kephart, G. M., Holley, K. E., and Gleich, G. J., 1982, Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma, Lancet ii:11–16.Google Scholar
  66. Findlay, S. R., Dvorak, A. M., Kagey-Sobotka, A., and Lichtenstein, L. M., 1981, Hyperosmolar triggering of histamine release from human basophils, J. Clin. Invest. 67: 1604–1613.PubMedGoogle Scholar
  67. Flaum, M. A., Schooley, R. T., Fauci, A. S., and Gralnick, H. R., 1981, A clinico-pathologic correlation of the idiopathic hypereosinophilic syndrome. I. Hematologic manifestations, Blood 58: 1012–1020.Google Scholar
  68. Fox, C. C., Dvorak, A. M., MacGlashan, Jr., D. W., and Lichtenstein, L. M., 1984, Histamine-containing cells in human peritoneal fluid, J. Immunol. 132: 2177–2179.PubMedGoogle Scholar
  69. Fredens, K., Dahl, R., and Venge, P., 1982, The Gordan phenomenon induced by the eosinophilic cationic protein and eosinophil protein X, J. Allergy Clin. Immunol. 70: 361–366.PubMedGoogle Scholar
  70. Galli, S. J., Dvorak, A. M., Peters, S. P., Schulman, E. S., MacGlashan, Jr., D. W., Isomura, T., Pyne, K., Harvey, V. S., Hammel, I., Lichtenstein, L. M., and Dvorak, H. F., 1985, Lipid bodies: Widely distributed cytoplasmic structures that represent preferential nonmembrane repositories of exogenous [3H]-arachidonic acid incorporated by mast cells, macrophages and other cell types, in Prostaglandins, Leukotrienes, and Lipoxins ( J. M. Bailey, ed.), pp. 221–239, Plenum Publishing Corp., New York.Google Scholar
  71. Gleich, G. J., Loegering, D. A., and Maldonado, J. E., 1973, Identification of major basic protein in guinea pig eosinophil granules, J. Exp. Med. 137: 1459–1471.PubMedGoogle Scholar
  72. Gleich, G. J., Loegering, D. A., Mann, K. G., and Maldonado, J. E., 1976, Comparative properties of the Charcot-Leyden crystal protein and the major basic protein from human eosinophils, J. Clin. Invest. 57: 633–640.PubMedGoogle Scholar
  73. Gleich, G. J., Frigas, E., Loegering, D. A., Wassom, D. C., and Steinmuller, D., 1979, Cytotoxic properties of the eosinophil major basic protein, J. Immunol. 123: 2925–2927.PubMedGoogle Scholar
  74. Hammel, I., Dvorak, A. M., Peters, S. P., Schulman, E. S., Dvorak, H. F., Lichtenstein, L. M., and Galli, S. J., 1985, Differences in the volume distributions of human lung mast cell granules and lipid bodies: Evidence that the size of these organelles is regulated by distinct mechanisms, J. Cell Biol. 100: 1488–1492.PubMedGoogle Scholar
  75. Hardin, J. H., and Spicer, S. S., 1970, An ultrastructural study of human eosinophil granules: Maturational stages and pyroantimonate reactive cation, Am. J. Anat. 128: 283–309.PubMedGoogle Scholar
  76. Harris, N. L., Dvorak, A. M., Smith, J., and Dvorak, H. F., 1982, Fibrin deposits in Hodgkin’s disease, Am. J. Pathol. 108: 119–129.PubMedGoogle Scholar
  77. Henderson, W. R., Jong, E. C., and Klebanoff, S. J., 1980, Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity, J. Immunol. 124: 1383–1388.PubMedGoogle Scholar
  78. Hudson, G., 1968, Cytoplasmic inclusions in eosinophil leukocytes: An electron microscope study of guinea pig bone marrow, J. Anat. 103: 337–343.PubMedGoogle Scholar
  79. Hyman, P. M., Teichberg, S., Starrett, S., Vinciguerra, V., and Degnan, T. J., 1978, Secretion of primary granules from developing human eosinophilic promyelocytes, Proc. Soc. Exp. Biol. Med. 159: 380–385.PubMedGoogle Scholar
  80. lozzo, R. V., MacDonald, G. H., and Wight, T. N., 1982, Immunoelectron microscopic localization of catalase in human eosinophilic leukocytes, J. Histochem. Cytochem. 30: 697–701.Google Scholar
  81. Ishizaka, T., Dvorak, A. M., Conrad, D. H., Niebyl, J. R., Marquette, J. P., and Ishizaka, K., 1985, Morphologic and immunologic characterization of human basophils developed in cultures of cord blood mononuclear cells, J. Immunol. 134: 532–540.PubMedGoogle Scholar
  82. Jabara, H. H., Ackerman, S. J., Vercelli, D., Yokota, T., Arai, K.-1., Abrams, J., Dvorak, A. M., Lavigne, M. C., Banchereau, J., DeVries, J., Leung, D. Y. M., and Geha, R. S., 1988, Induction of interleukin 4dependent IgE synthesis and interleukin 5-dependent eosinophil differentiation by supernatants of a human helper T cell clone, J. Clin. Immunol. 8: 437–446.Google Scholar
  83. Jong, E. C., and Klebanoff, S. J., 1980, Eosinophil-mediated mammalian tumor cell cytotoxicity: Role of the peroxidase system, J. Immunol. 124: 1949–1953.PubMedGoogle Scholar
  84. Jong, E. C., Henderson, W. R., and Klebanoff, S. J., 1980, Bactericidal activity of eosinophil peroxidase, J. Immunol. 124: 1378–1382.PubMedGoogle Scholar
  85. Kazura, J. W., and Aikawa, M., 1980, Host defense mechanisms against Trichinella spiralis infection in the mouse: Eosinophil-mediated destruction of newborn larvae in vitro, J. Immunol. 124: 355–361.PubMedGoogle Scholar
  86. Kephart, G. M., Gleich, G. J., Connor, D. H., Gibson, D. W., and Ackerman, S. J., 1984, Deposition of eosinophil granule major basic protein onto microfilariae of Onchocerca volvulus in the skin of patients treated with diethylcarbamazine, Lab. Invest. 50: 51–61.PubMedGoogle Scholar
  87. Kimmenad, A., Bond, M. W., Schumacher, J. H., Laquoi, C., and Kastelein, R. A., 1988, Expression, renaturation and purification of recombinant human interleukin 4 from Escherichia coli, Eur. J. Biochem. 173: 109–114.Google Scholar
  88. Komiyama, A., and Spicer, S. S., 1975, Microendocytosis in eosinophilic leukocytes, J. Cell Biol. 64: 622–635.PubMedGoogle Scholar
  89. Le, H. V., Ramanathan, L., Labdon, J. E., Mays-Ichinco, C. A., Syto, R., Arai, N., Hoy, P., Takebe, Y., Nagabhushan, T. L., and Trotta, P. P., 1988, Isolation and characterization of multiple variants of recombinant human interleukin 4 expressed in mammalian cells, J. Biol. Chem. 263: 10817–10823.PubMedGoogle Scholar
  90. Leiferman, K. M., Ackerman, S. J., Sampson, H. A., Haugen, H. S., Venencie, P. Y., and Gleich, G. J., 1985, Dermal deposition of eosinophil major basic protein in atopic dermatitis, N. Engl. J. Med. 313: 282–285.PubMedGoogle Scholar
  91. Lewis, D. M., Lewis, J. C., Loegering, D. A., and Gleich, G. J., 1978, Localization of the guinea pig eosinophil major basic protein to the core of the granule, J. Cell Biol. 77: 702–713.PubMedGoogle Scholar
  92. Leyden, E., 1872, Zur Kenntnis des Bronchial-Asthma, Arch. Pathol. Anat. 54: 324–352.Google Scholar
  93. Lopez, A. F., Sanderson, C. J., Gamble, J. R., Campbell, H. D., Young, I. G., and Vadas, M. A., 1988, Recombinant human interleukin 5 is a selective activator of human eosinophil function, J. Exp. Med. 167: 219–224.PubMedGoogle Scholar
  94. Lucey, D. R., Dorsky, D. I., Nicholson-Weller, A., and Weller, P. F., 1989a, Human eosinophils express CD4 protein and bind HIV-1 GP120, J. Exp. Med. 169: 327–332.PubMedGoogle Scholar
  95. Lucey, D. R., Nicholson-Weller, A., and Weller, P. F., 1989b, Mature human eosinophils have the capacity to express HLA-DR, Proc. Natl. Acad. Sci. USA 86: 1348–1351.PubMedGoogle Scholar
  96. MacMillan, R. H., Cooper, P. H., Body, B. A., and Mills, A. S., 1987, Allergic fungal sinusitis due to Curvularia Iunata, Hum. Pathol. 18: 960–964.PubMedGoogle Scholar
  97. McLaren, D. J., Ralmalho-Pinto, F. J., and Smithers, S. R., 1978, Ultrastructural evidence of complement and antibody-dependent damage to schistosomula of Schistosoma monsoni by rat eosinophils in vitro, Parasitology 77: 313–324.PubMedGoogle Scholar
  98. Migler, R., DeChatelet, L. R., and Bass, D. A., 1978, Human eosinophilic peroxidase: Role in bactericidal activity, Blood 51: 445–456.PubMedGoogle Scholar
  99. Miller, F., DeHarven, E., and Palade, G. E., 1966, The structure of eosinophilic leukocyte granules in rodents and in man, J. Cell Biol. 31: 349–362.PubMedGoogle Scholar
  100. Monahan, R. A., Dvorak, H. F., and Dvorak, A. M., 1981, Ultrastructural localization of nonspecific esterase activity in guinea pig and human monocytes, macrophages, and lymphocytes, Blood 58: 1089–1099.PubMedGoogle Scholar
  101. Mosmann, T. R., Cherwinski, H, Bond, M. W., Giedlin, M., and Coffman, R. L., 1986, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, J. Immunol. 136: 2348–2357.PubMedGoogle Scholar
  102. Nabel, G., Galli, S. J., Dvorak, A. M., Dvorak, H. F., and Cantor, H., 1981a, Inducer T lymphocytes synthesize a factor that stimulates proliferation of cloned mast cells, London (London) 291: 332–334.Google Scholar
  103. Nabel, G., Greenberger, J. S., Sakakeeny, M. A., and Cantor, H., 1981b, Multiple biologic activities of a cloned inducer T-cell population, Proc. Natl. Acad. Sci. USA 78: 1157–1161.PubMedGoogle Scholar
  104. Nathan, C. F., and Klebanoff, S. J., 1982, Augmentation of spontaneous macrophage-mediated cytolysis by eosinophil peroxidase, J. Exp. Med. 155: 1291–1308.PubMedGoogle Scholar
  105. Ogawa, M., Nakahata, T., Leary, A. G., Sterk, A. R., Ishizaka, K., and Ishizaka, T., 1983, Suspension culture of human mast cells/basophils from umbilical cord blood mononuclear cells, Proc. Natl. Acad. Sci. USA 80: 4494–4498.PubMedGoogle Scholar
  106. Okuda, M., Takenaka, T., Kawabori, S., and Ogami, Y., 1981, Ultrastructural study of the specific granule of the human eosinophil, J. Submicrosc. Cytol. 13: 465–471.PubMedGoogle Scholar
  107. Olsson, I., Persson, A.-M., and Winqvist, I., 1986, Biochemical properties of the eosinophil cationic protein and demonstration of its biosynthesis in vitro in marrow cells from patients with eosinophilia, Blood 67: 498–503.PubMedGoogle Scholar
  108. Otsuka, T., Miyajima, A., Brown, N., Otsu, K., Abrams, J., Sealand, S., Caux, C., Malefijt, R. D., DeVries, J., Meyerson, P., Yokota, K., Gemmel, L., Rennick, D. M., Lee, F. D., Arai, N., Arai, K., and Yokota, T., 1987, Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones, J. Immunol. 140: 2288–2295.Google Scholar
  109. Ottesen, E. A., and Cohen, S. G., 1978, The eosinophil, eosinophilia and eosinophil-related disorders, Allergy: Principles and Practice, Vol. 2 (E. Middleton, C. E. Reed, and E. F. Ellis, eds.), pp. 584–632, C. V. Mosby Co., St. Louis.Google Scholar
  110. Parmley, R. T., and Spicer, S. S., 1974, Cytochemical and ultrastructural identification of a small type granule in human late eosinophils, Lab. Invest. 30: 557–567.PubMedGoogle Scholar
  111. Parmley, R. T., and Spicer, S. S., 1975, Altered tissue eosinophils in Hodgkin’s disease, Exp. Mol. Pathol. 23: 70–82.PubMedGoogle Scholar
  112. Peters, M., Rodreguez, M., and Gleich, G., 1986, Localization of human eosinophil granule major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin by immunoelectron microscopy, Lab. Invest. 54: 656–662.PubMedGoogle Scholar
  113. Peters, M. S., Schroeter, A. L., Kephart, G. M., and Gleich, G. J., 1983, Localization of eosinophil major basic protein in chronic urticaria, J. Invest. Dermatol. 81: 39–43.PubMedGoogle Scholar
  114. Peters, M. S., Gleich, G. J., Dunnette, S. L., and Fukuda, T., 1988, Ultrastructural study of eosinophils from patients with the hypereosinophilic syndrome: A morphological basis of hypodense eosinophils, Blood 71: 780–785.PubMedGoogle Scholar
  115. Ramsey, P. G., Martin, T., Chi, E., and Klebanoff, S. J., 1982, Arming of mononuclear phagocytes by eosinophil bound to Staphylococcus aureus, J. Immunol. 128: 415–420.PubMedGoogle Scholar
  116. Ross, R., and Klebanoff, S. J., 1966, The eosinophilic leukocyte. Fine structure studies of changes in the uterus during the estrous cycle, J. Exp. Med. 124: 653–681.PubMedGoogle Scholar
  117. Saito, H., Hatake, K., Dvorak, A. M., Leiferman, K. M., Donnenberg, A. D., Arai, N., Ishizaka, K., and Ishizaka, T., 1988, Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins, Proc. Natl. Acad. Sci. USA 85: 2288–2292.PubMedGoogle Scholar
  118. Samoszuk, M. K., Nathwani, B. N., and Lukes, R. J., 1986, Extensive deposition of eosinophil peroxidase in Hodgkin’s and non-Hodgkin’s lymphomas, Am. J. Pathol. 125: 426–429.PubMedGoogle Scholar
  119. Samoszuk, M., Sholly, S., and Epstein, A. L., 1987, Eosinophil peroxidase is detectable with a monoclonal antibody in collagen bands of nodular sclerosis Hodgkin’s disease, Lab. Invest. 56: 394–400.PubMedGoogle Scholar
  120. Sanderson, C. J., Warren, D. J., and Strath, M., 1985, Identification of a lymphokine that stimulates eosinophil differential in vitro. Its relationship to interleukin-3 and functional properties of eosinophils produced in culture. J. Exp. Med. 162: 60–74.PubMedGoogle Scholar
  121. Schaefer, H. E., Hubner, G., and Fischer, R., 1973, Spezifische Mikrogranula in Eosinophilen, Acta Haematol. 50: 92–104.PubMedGoogle Scholar
  122. Scott, R. E., and Horn, R. G., 1970, Fine structural features of eosinophil granulocyte development in bone marrow. Evidence for granule secretion, J. Ultrastruct. Res. 33: 16–28.PubMedGoogle Scholar
  123. Seeman, P. M., and Palade, G. E., 1967, Acid phosphatase localization in rabbit eosinophils, J. Cell Biol. 34: 745–756.PubMedGoogle Scholar
  124. Skinnider, L. F., and Ghadially, F. N., 1974, Secretion of granule content by eosinophils, Arch. Pathol. 98: 5861.Google Scholar
  125. Spry, C. J. F., Tai, P.-C., and Barkans, J., 1985, Tissue localization of human eosinophil cationic proteins in allergic diseases, Int. Arch. Allergy Appl. Immunol. 77: 252–254.PubMedGoogle Scholar
  126. Tai, P.-C., and Spry, C. J. F., 1981, The mechanisms which produce vacuolated and degranulated eosinophils, Br. J. Haematol. 49: 219–226.PubMedGoogle Scholar
  127. Tai, P.-C., Holt, M. E., Denny, P., Gibbs, A. R., Williams, B. D., and Spry, C. J. F., 1984a, Deposition of eosinophil cationic protein in granulomas in allergic granulomatosis and vasculitis: The Churg-Strauss syndrome, Br. Med. J. 289: 400–402.Google Scholar
  128. Tai, P.-C., Spry, C. J. F., Peterson, C., Venge, P., and Olsson, I., 1984b, Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein, Nature (London) 309: 182–184.Google Scholar
  129. Tai, P.-C., Spry, C. J. F., Olsen, E. G. J., Ackerman, S. J., Dunnette, S., and Gleich, G. J., 1987, Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease, Lancet 1: 643–647.PubMedGoogle Scholar
  130. Takebe, Y., Seiki, M., Fujisawa, J., Hoy, P., Yokota, K., Arai, K., Yoshida, M., and Arai, N., 1988, SRa promoter: An efficient and versatile mamalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long term repeat, Mol. Cell. Biol. 8: 466–472.PubMedGoogle Scholar
  131. Thompson, J. H., and Paddock, F. K., 1940, The significance of Charcot-Leyden crystals, N. Engl. J. Med. 223: 936–939.Google Scholar
  132. Weller, P. F., and Austen, K. F., 1983, Human eosinophil arylsulfatase B—structure and activity of the purified tetrameric lysosomal hydrolase, J. Clin. Invest. 71: 114–123.PubMedGoogle Scholar
  133. Weller, P. F., and Dvorak, A. M., 1985, Arachidonic and incorporation by cytoplasmic lipid bodies of human eosinophils, Blood 65: 1269–1274.PubMedGoogle Scholar
  134. Weller, P. F., Goetzl, E. J., and Austen, K. F., 1980, Identification of human eosinophil lysophospholipase as the constituent of Charcot-Leyden crystals, Proc. Natl. Acad. Sci. USA 77: 7440–7443.PubMedGoogle Scholar
  135. Weller, P. F., Bach, D. S., and Austen, K. F., 1982, Human eosinophil lysophospholipase: The sole protein component of Charcot-Leyden crystals, J. lmmunol. 128: 1346–1349.Google Scholar
  136. Weller, P. F., Bach, D. S., and Austen, K. F., 1984, Biochemical characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase), J. Biol. Chem. 259: 15100–15105.PubMedGoogle Scholar
  137. Weller, P. F., Ackerman, S. J., Nicholson-Weller, A., and Dvorak, A. M., 1989, Cytoplasmic lipid bodies of human neutrophilic leukocytes, Am. J. Pathol. 135: 947–959.PubMedGoogle Scholar
  138. Welsh, R. A., 1959, The genesis of Charcot-Leyden crystal in the eosinophilic leukocyte in man, Am. J. Pathol. 35: 1091–1103.PubMedGoogle Scholar
  139. West, B. C., Gelb, N. A., and Rosenthal, A. S., 1975, Isolation and partial characterization of human eosinophil granules, Am. J. Pathol. 135: 947–959.Google Scholar
  140. Wetzel, B. K., Horn, R. G., and Spicer, S. S., 1967, Fine structural studies on the development of heterophil, eosinophil, and basophil granulocytes in rabbits, Lab. Invest. 16: 349–382.PubMedGoogle Scholar
  141. Yamaguchi, Y., Hayashi, Y., Sugama, Y., Miura, Y., Kasahara, T., Kitamura, S., Torisu, M., Mita, S., Tominaga, A., Takatsu, K., and Suda, T., 1988a, Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor, J. Exp. Med. 167: 1737–1742.PubMedGoogle Scholar
  142. Yamaguchi, Y., Suda, T., Suda, J., Eguchi, M., Miura, Y., Harada, N., Tominaga, A., and Takatsu, K., 1988b, Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophil precursors, J. Exp. Med. 167: 43–56.PubMedGoogle Scholar
  143. Yokota, S., and Oda, T., 1983, Immunoelectron microscopic localization of serine:pyruvate aminotransferase in rat eosinophil leukocytes, Histochemistry 78: 417–424.PubMedGoogle Scholar
  144. Yokota, S., Deimann, W., Hashimoto, T., Fahimi, H. D., 1983, Immunocytochemical localization of two peroxisomal enzymes in lipid beta-oxidation in specific granules of rat eosinophils, Histochemistry 78: 425–433.PubMedGoogle Scholar
  145. Yokota, S., Deimann, W., Hashimoto, T., and Fahimi, H. D., 1984a, Specific granules of rat eosinophils contain peroxisomal acyl-CoA oxidase: Possible involvement in production of H2O2, Histochem. J. 16: 573–577.PubMedGoogle Scholar
  146. Yokota, S., Tsuji, H., and Kato, K., 1984b, Localization of lysosomal and peroxisomal enzymes in the specific granules of rat intestinal eosinophil leukocytes revealed by immunoelectron microscopic techniques, J. Histochem. Cytochem. 32: 267–274.PubMedGoogle Scholar
  147. Yokota, T., Lee, F., Rennick, D., Hall, C., Arai, N., Mosmann, T., Nabel, G., Cantor, H., and Arai, K., 1984, Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells, Proc. Natl. Acad. Sci. USA 81: 1070–1074.PubMedGoogle Scholar
  148. Yokota, T., Coffman, R. L., Hagiwara, H., Rennick, D. M., Takebe, Y., Yokota, K., Gemmel., L., Shrader, B., Yang, G., Meyerson, P., Luh, J., Hoy, P., Pene, J., Briere, F., Spits, H., Banchereau, J., DeVries, J., Lee, F. D., Arai, N., and Arai, K.-I., 1987, Isolation and characterization of lymphokine cDNA clones encoding mouse and human IgA-enhancing factor and eosinophil colony-stimulating factor activities: Relationship to interleukin 5, Proc. Natl. Acad. Sci. USA 84: 7388–7392.PubMedGoogle Scholar
  149. Young, J. D.-E., Peterson, C. G. B., Venge, P., and Cohn, Z. A., 1986, Mechanism of membrane damage mediated by human eosinophilic cationic protein, Nature (London) 321: 613–616.Google Scholar
  150. Zipori, D., Tamir, M., Toledo, J., and Oren, T., 1986, Differentiation stage and lineage-specific inhibitor from the stroma of mouse bone marrow that restricts lymphoma cell growth, Proc. Natl. Acad. Sci. USA 83: 4547–4551.PubMedGoogle Scholar
  151. Zucker-Franklin, D., 1980, Eosinophil structure and function, in The Eosinophil in Health and Disease ( A. A. F. Mahmoud and K. F. Austen, eds.), pp. 43–59, Grune and Stratton, New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • A. M. Dvorak
    • 1
  • S. J. Ackerman
    • 1
  • P. F. Weller
    • 1
  1. 1.Departments of Pathology and Medicine, Beth Israel Hospital and Harvard Medical School, and Charles A. Dana Research InstitutueBeth Israel HospitalBostonUSA

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