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Contributions of Electron Microscopy to Understand Secretion of Immune Mediators by Human Eosinophils

Published online by Cambridge University Press:  27 September 2010

Rossana C.N. Melo ,
Ann M. Dvorak  and
Peter F. Weller
Rossana C.N. Melo*
Affiliation:
Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, UFJF, Juiz de Fora, MG, Brazil Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Ann M. Dvorak
Affiliation:
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Peter F. Weller
Affiliation:
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
*
Corresponding author. E-mail: [email protected]
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Abstract

Mechanisms governing secretion of proteins underlie the biologic activities and functions of human eosinophils, leukocytes of the innate immune system, involved in allergic, inflammatory, and immunoregulatory responses. In response to varied stimuli, eosinophils are recruited from the circulation into inflammatory foci, where they modulate immune responses through the release of granule-derived products. Transmission electron microscopy (TEM) is the only technique that can clearly identify and distinguish between different modes of cell secretion. In this review, we highlight the advances in understanding mechanisms of eosinophil secretion, based on TEM findings, that have been made over the past years and that have provided unprecedented insights into the functional capabilities of these cells.

Keywords

transmission electron microscopyelectron tomographyeosinophilscell secretionvesicular transportinflammationimmune systemcytokines
Type
Review Article
Information
Microscopy and Microanalysis , Volume 16 , Issue 6 , December 2010 , pp. 653 - 660
Copyright
Copyright © Microscopy Society of America 2010

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References

REFERENCES

Ackerman, S.J. & Bochner, B.S. (2007). Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. Immunol Allergy Clin North Am 27(3), 357–375.CrossRefGoogle ScholarPubMed
Adamko, D.J., Odemuyiwa, S.O., Vethanayagam, D. & Moqbel, R. (2005). The rise of the phoenix: The expanding role of the eosinophil in health and disease. Allergy 60(1), 13–22.CrossRefGoogle ScholarPubMed
Ahlstrom-Emanuelsson, C.A., Greiff, L., Andersson, M., Persson, C.G. & Erjefalt, J.S. (2004). Eosinophil degranulation status in allergic rhinitis: Observations before and during seasonal allergen exposure. Eur Respir J 24(5), 750–757.CrossRefGoogle ScholarPubMed
Akuthota, P., Wang, H.B., Spencer, L.A. & Weller, P.F. (2008). Immunoregulatory roles of eosinophils: A new look at a familiar cell. Clin Exp Allergy 38(8), 1254–1263.CrossRefGoogle Scholar
Armengot, M., Garin, L. & Carda, C. (2009). Eosinophil degranulation patterns in nasal polyposis: An ultrastructural study. Am J Rhinol Allergy 23(5), 466–470.CrossRefGoogle ScholarPubMed
Bandeira-Melo, C., Perez, S.A.C., Melo, R.C.N., Ghiran, I. & Weller, P.F. (2003). EliCell assay for the detection of released cytokines from eosinophils. J Immunol Methods 276(1–2), 227–237.Google Scholar
Bandeira-Melo, C., Sugiyama, K., Woods, L.J. & Weller, P.F. (2001). Cutting edge: Eotaxin elicits rapid vesicular transport-mediated release of preformed IL-4 from human eosinophils. J Immunol 166(8), 4813–4817.CrossRefGoogle ScholarPubMed
Beil, W.J., Weller, P.F., Tzizik, D.M., Galli, S.J. & Dvorak, A.M. (1993). Ultrastructural immunogold localization of tumor necrosis factor-alpha to the matrix compartment of eosinophil secondary granules in patients with idiopathic hypereosinophilic syndrome. J Histochem Cytochem 41(11), 1611–1615.CrossRefGoogle Scholar
Dvorak, A.M. (1992). Human mast cells. Ultrastructural observations of in situ, ex vivo, in vitro studies, sources, systems. In The Mast Cell in Health and Disease, Kaliner, M.A. & Metcalfe, D.D. (Eds.), pp. 1–90. New York: Marcel Dekker.Google Scholar
Dvorak, A.M., Furitsu, T., Letourneau, L., Ishizaka, T. & Ackerman, S.J. (1991). Mature eosinophils stimulated to develop in human cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. I. Piecemeal degranulation of specific granules and distribution of Charcot-Leyden crystal protein. Am J Pathol 138(1), 69–82.Google ScholarPubMed
Dvorak, A.M., Monahan, R.A., Osage, J.E. & Dickersin, G.R. (1980). Crohn's disease: Transmission electron microscopic studies. II. Immunologic inflammatory response. Alterations of mast cells, basophils, eosinophils, and the microvasculature. Hum Pathol 11(6), 606–619.CrossRefGoogle ScholarPubMed
Dvorak, A.M. & Weller, P.F. (2000). Ultrastructural analysis of human eosinophils. In Human Eosinophils: Biological and Chemical Aspects, Marone, G. (Ed.), pp. 1–28. Basel: Karger.Google Scholar
Egesten, A., Calafat, J., Knol, E.F., Janssen, H. & Walz, T.M. (1996). Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes. Blood 87(9), 3910–3918.Google Scholar
Erjefalt, J.S., Greiff, L., Andersson, M., Adelroth, E., Jeffery, P.K. & Persson, C.G. (2001). Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease. Thorax 56(5), 341–344.Google Scholar
Erjefalt, J.S. & Persson, C.G. (2000). New aspects of degranulation and fates of airway mucosal eosinophils. Am J Respir Crit Care Med 161(6), 2074–2085.Google Scholar
Gleich, G.J. (2000). Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol 105(4), 651–663.CrossRefGoogle ScholarPubMed
Hogan, S.P., Rosenberg, H.F., Moqbel, R., Phipps, S., Foster, P.S., Lacy, P., Kay, A.B. & Rothenberg, M.E. (2008). Eosinophils: Biological properties and role in health and disease. Clin Exp Allergy 38(5), 709–750.CrossRefGoogle ScholarPubMed
Jamieson, J.D. & Palade, G.E. (1967). Intracellular transport of secretory proteins in the pancreatic exocrine cell. II. Transport to condensing vacuoles and zymogen granules. J Cell Biol 34(2), 597–615.Google Scholar
Karawajczyk, M., Seveus, L., Garcia, R., Bjornsson, E., Peterson, C.G., Roomans, G.M. & Venge, P. (2000). Piecemeal degranulation of peripheral blood eosinophils: A study of allergic subjects during and out of the pollen season. Am J Respir Cell Mol Biol 23(4), 521–529.CrossRefGoogle ScholarPubMed
Komiyama, A. & Spicer, S.S. (1975). Microendocytosis in eosinophilic leukocytes. J Cell Biol 64(3), 622–635.CrossRefGoogle ScholarPubMed
Kroegel, C., Dewar, A., Yukawa, T., Venge, P., Barnes, P.J. & Chung, K.F. (1993). Ultrastructural characterization of platelet-activating factor-stimulated human eosinophils from patients with asthma. Clin Sci (Lond) 84(4), 391–399.CrossRefGoogle ScholarPubMed
Lacy, P., Mahmudi-Azer, S., Bablitz, B., Hagen, S.C., Velazquez, J.R., Man, S.F. & Moqbel, R. (1999). Rapid mobilization of intracellularly stored RANTES in response to interferon-gamma in human eosinophils. Blood 94(1), 23–32.Google Scholar
Luini, A., Ragnini-Wilson, A., Polishchuck, R.S. & De Matteis, M.A. (2005). Large pleiomorphic traffic intermediates in the secretory pathway. Curr Opin Cell Biol 17(4), 353–361.Google Scholar
Manderson, A.P., Kay, J.G., Hammond, L.A., Brown, D.L. & Stow, J.L. (2007). Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNF{alpha}. J Cell Biol 178(1), 57–69.CrossRefGoogle Scholar
Melo, R.C.N., Dvorak, A.M. & Weller, P.F. (2008a). Electron tomography and immunonanogold electron microscopy for investigating intracellular trafficking and secretion in human eosinophils. J Cell Mol Med 12(4), 1416–1419.Google Scholar
Melo, R.C.N., Dvorak, A.M. & Weller, P.F. (2008b). New aspects of piecemeal degranulation in human eosinophils. In New Research in Innate Immunity, pp. 329–348. Hauppauge, NY: Nova Science Publishers.Google Scholar
Melo, R.C.N., Perez, S.A.C., Spencer, L.A., Dvorak, A.M. & Weller, P.F. (2005a). Intragranular vesiculotubular compartments are involved in piecemeal degranulation by activated human eosinophils. Traffic 6(10), 866–879.CrossRefGoogle ScholarPubMed
Melo, R.C.N., Sabban, A. & Weller, P.F. (2006). Leukocyte lipid bodies: Inflammation-related organelles are rapidly detected by wet scanning electron microscopy. J Lipid Res 47(11), 2589–2594.CrossRefGoogle ScholarPubMed
Melo, R.C.N., Spencer, L.A., Dvorak, A.M. & Weller, P.F. (2008c). Mechanisms of eosinophil secretion: Large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins. J Leukoc Biol 83(2), 229–236.CrossRefGoogle ScholarPubMed
Melo, R.C.N., Spencer, L.A., Perez, S.A.C., Ghiran, I., Dvorak, A.M. & Weller, P.F. (2005b). Human eosinophils secrete preformed, granule-stored interleukin-4 (IL-4) through distinct vesicular compartments. Traffic 6(11), 1047–1057.CrossRefGoogle ScholarPubMed
Melo, R.C.N., Spencer, L.A., Perez, S.A., Neves, J.S., Bafford, S.P., Morgan, E.S., Dvorak, A.M. & Weller, P.F. (2009). Vesicle-mediated secretion of human eosinophil granule-derived major basic protein. Lab Invest 89(7), 769–781.Google Scholar
Melo, R.C.N. & Weller, P.F. (2010). Piecemeal degranulation in human eosinophils: a distinct secretion mechanism underlying inflammatory responses. Histology & Histopathology 25(10), 1341–1354.Google Scholar
Melo, R.C.N., Weller, P.F. & Dvorak, A.M. (2005c). Activated human eosinophils. Int Arch Allergy Immunol 138(4), 347–349.Google Scholar
Moller, G.M., de Jong, T.A., van der Kwast, T.H., Overbeek, S.E., Wierenga-Wolf, A.F., Thepen, T. & Hoogsteden, H.C. (1996). Immunolocalization of interleukin-4 in eosinophils in the bronchial mucosa of atopic asthmatics. Am J Respir Cell Mol Biol 14(5), 439–443.Google Scholar
Moqbel, R. & Coughlin, J.J. (2006). Differential secretion of cytokines. Sci STKE 2006 (338), pe26.Google Scholar
Moqbel, R., Ying, S., Barkans, J., Newman, T.M., Kimmitt, P., Wakelin, M., Taborda-Barata, L., Meng, Q., Corrigan, C.J., Durham, S.R. & Kay, A.B. (1995). Identification of messenger RNA for IL-4 in human eosinophils with granule localization and release of the translated product. J Immunol 155(10), 4939–4947.CrossRefGoogle ScholarPubMed
Nebenfuhr, A., Ritzenthaler, C. & Robinson, D.G. (2002). Brefeldin A: Deciphering an enigmatic inhibitor of secretion. Plant Physiol 130(3), 1102–1108.CrossRefGoogle ScholarPubMed
Okuda, M., Takenaka, T., Kawabori, S. & Ogami, Y. (1981). Ultrastructural study of the specific granule of the human eosinophil. J Submicrosc Cytol 13(3), 465–471.Google Scholar
Oliveira, S.H., Taub, D.D., Nagel, J., Smith, R., Hogaboam, C.M., Berlin, A. & Lukacs, N.W. (2002). Stem cell factor induces eosinophil activation and degranulation: Mediator release and gene array analysis. Blood 100(13), 4291–4297.Google Scholar
Simpson, J.C., Nilsson, T. & Pepperkok, R. (2006). Biogenesis of tubular ER-to-Golgi transport intermediates. Mol Biol Cell 17(2), 723–737.CrossRefGoogle ScholarPubMed
Specht, S., Saeftel, M., Arndt, M., Endl, E., Dubben, B., Lee, N.A., Lee, J.J. & Hoerauf, A. (2006). Lack of eosinophil peroxidase or major basic protein impairs defense against murine filarial infection. Infect Immun 74(9), 5236–5243.CrossRefGoogle ScholarPubMed
Spencer, L.A., Melo, R.C.N., Perez, S.A., Bafford, S.P., Dvorak, A.M. & Weller, P.F. (2006). Cytokine receptor-mediated trafficking of preformed IL-4 in eosinophils identifies an innate immune mechanism of cytokine secretion. Proc Natl Acad Sci USA 103(9), 3333–3338.CrossRefGoogle ScholarPubMed
Spencer, L.A., Szela, C.T., Perez, S.A., Kirchhoffer, C.L., Neves, J.S., Radke, A.L. & Weller, P.F. (2009). Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially. J Leukoc Biol 85(1), 117–123.Google Scholar
Stow, J.L., Ching Low, P., Offenhauser, C. & Sangermani, D. (2009). Cytokine secretion in macrophages and other cells: Pathways and mediators. Immunobiology 214(7), 601–612.Google Scholar
Tai, P.C., Ackerman, S.J., Spry, C.J., Dunnette, S., Olsen, E.G. & Gleich, G.J. (1987). Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. Lancet 1(8534), 643–647.Google Scholar
Watson, P. & Stephens, D.J. (2005). ER-to-Golgi transport: Form and formation of vesicular and tubular carriers. Biochim Biophys Acta 1744(3), 304–315.Google Scholar
Weller, P.F., Neves, J.S., Perez, S.A., Melo, R.C.N., Spencer, L.A. & Dvorak, A.M. (2009). Mechanisms of human eosinophil secretion. Cytokine 48(1–2), 40.CrossRefGoogle Scholar
Zetterstrom, R. (2006). A. Claude (1899–1983), C. de Duve (1917–) and G.E. Palade (1912–): Nobel Prize for discoveries in integrated cell physiology. Clarification of aetiology and pathogenesis of a great number of diseases. Acta Paediatr 95(12), 1523–1525.Google Scholar