Summary
Clusters of luminal dense bodies, limited by a triple-layered membrane, were found in all follicle lumina in thyroid glands of mice. After thyroxine treatment the number of luminal dense bodies increased, especially in the periphery of the lumen, where the intraluminal bodies often displayed a striking resemblance to microvilli. In hyperplastic goiters, obtained by feeding mice with propylthiouracil, luminal dense bodies were replaced by intraluminal vesicles. During goiter involution the vesicles were gradually replaced by luminal dense bodies; the presence of intermediate forms suggests that vesicles and dense bodies are basically the same formations. Luminal dense bodies were observed in colloid droplets indicating their removal by endocytosis. As demonstrated by electron-microscopic cytochemistry, luminal dense bodies contain a membranebound peroxidase, and electron-microscopic autoradiography after administration of 125I indicate that they possess an iodinating capacity.
Our observations on mouse thyroid glands suggest that the luminal dense bodies, which appear as vesicles in hyperplastic glands, are formed by shedding of the apical plasma membrane of the follicle cell. The shedding process might be of importance for the turnover of plasma-membrane material.
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Allan D, Billah MM, Finean IB, Michell RH (1976) Release of diacylglycerol-enriched vesicles from erythrocytes with increased intracellular (Ca2+). Nature 261:58–60
Bab I, Rosenmann E, Néeman Z, Sela J (1981) The occurrence of extracellular matrix vesicles in pulmonary alveolar microlithiasis. Virchows Arch [Pathol Anat] 391:357–361
Biberfeld P, Biberfeld G, Perlmann P, Holm G (1973) Cytological observations on the cytotoxic interaction between lymphocytes and antibody-coated monolayer cells. Cell Immunol 7:60–72
Billington D, Coleman R (1978) Effects of bile salts on human erythrocytes. Plasma membrane vesiculation, phospholipid solubilization and their possible relationships to bile secretion. Biochim Biophys Acta 509:33–47
Björkman U, Ekholm R, Elmqvist L-G, Ericson LE, Melander A, Smeds S (1974) Induced unidirectional transport of protein into the thyroid follicular lumen. Endocrinology 95:1506–1517
Björkman U, Ekholm R, Ericson LE, Öfverholm T (1976) Transport of thyroglobulin and peroxidase in the thyroid follicle cell. Mol Cell Endocrinol 5:3–17
Black PH (1980) Shedding from the surface of normal and cancer cells. Adv Cancer Res 32:75–199
Black BL, Yoneyama Y, Moog F (1980) Microvillous membrane vesicle accumulation in media during culture of intestine of chick embryo. Biochim Biophys Acta 601:343–348
Boivin PG (1975) Cutaneous calcinosis induced by topical calciphylaxis in the rat. 1. Ultrastructural aspects. Arch Anat Microsc 64:183–205
Bonucci E (1970) Fine structure and histochemistry of “calcifying globules” in epiphyseal cartilage. Z Zellforsch 103:192–217
Cone RE (1977) Dynamic aspects of the lymphocyte surface. In: Marchalonis II (ed) The lymphocyte: structure and function vol 2. Dekker, NY, pp 565–592
Cossel L (1980) Peripheral cytoplasmic shedding around hepatocytes-apocrine secretion, pathological cell reaction or preparation artefact? Pathol Res Pract 170:298–327
Dainiak N, Cohen CM (1982) Surface membrane vesicles from mononuclear cells stimulate erythroid stem cells to proliferate in culture. Blood 60:583–594
DeBroe ME, Borgers M, Wieme RJ (1975) The separation and characterization of liver plasma membrane fragments circulating in the blood of patients with cholestasis. Clin Chim Acta 59:369–372
DeBroe ME, Wieme RJ, Logghe GN, Roels F (1977) Spontaneous shedding of plasma membrane fragments by human cells in vivo and in vitro. Clin Chim Acta 81:237–245
DeRitis G, Falchuk ZM, Trier JS (1975) Differentiation and maturation of cultured fetal rat jejunum. Dev Biol 45:304–317
Doljanski F, Kapeller M (1976) Cell surface shedding — the phenomenon and its possible significance. J Theor Biol 62:253–270
Doyle JJ, Behin R, Manuel J, Rowe DS (1974) Antibody-induced movement of membrane components of Leishmania enriettii. J Exp Med 139:1061–1069
Dvorak HF, Quay SC, Orenstein NS, Dvorak AM, Hahn P, Bitzer AM (1981) Tumor shedding and coagulation. Science 212:923–924
Ekholm R (1981) Iodination of thyroglobulin — an intracellular or extracellular process? Mol Cel Endocrinol 24:141–163
Ekholm R, Wollman SH (1975) Site of iodination in rat thyroid gland deduced from electron microscopic autoradiographs. Endocrinology 97:1432–1444
Ekholm R, Engström G, Ericson LE, Melander A (1975) Exocytosis of protein into thyroid follicle lumen: an early effect of TSH. Endocrinology 97:337–346
Emerson SG, Cone RE (1981) I-Kk and H-2Kk antigens are shed as supramolecular particles in association with membrane lipids. J Immunol 127:482–486
Emerson SG, Cone RE (1982) Absorption of shed I-Ak and H-2Kk antigen by lymphoid cells. Transplantation 33:36–40
Ericson LE (1981) Exocytosis and endocytosis in the thyroid follicle cell. Mol Cell Endocrinol 22:1–24
Ericson LE, Johanson V (1981) Turnover of exocytotic vesicles in rat thyroid follicle cells. Ann d'endocrinologie A. Abstr 11th Annual Meeting of the European Thyroid Association, Pisa p 77
Esselman WJ, Miller HC (1977) Modulation of B cell responses by glycolipid released from antigen-stimulated T cells. J Immunol 119:1994–2000
Ferber E, Schmidt B, Weltzien HU (1980) Spontaneous and detergent-induced vesiculation of thymocyte plasma membranes. Biochim Biophys Acta 595:244–256
Freimuth WW, Esselman WJ, Miller HC (1978) Release of Thy-1.2 and Thy-1.1 from lymphoblastoid cells: partial characterization and antigenicity of shed material. J Immunol 120:1651–1658
Gasic GJ, Gasic TB (1982) Plasma membrane vesicles as mediators of interactions between tumor cells and components of the hemostatic and immune systems. In: Interaction of platelets and tumor cells. Alan R Liss Inc, New York, pp 429–444
Godman GC, Miranda AF, Deitch AD, Tanenbaum SW (1975) Action of cytochalasin D on cells of established lines. III. Zeiosis and movements at the cell surface. J Cell Biol 64:644–667
Golub EE, Schattschneider S, McArthur WP, Burke A, Shapiro IM (1981) Induction of vesiculation by cultured chondrocytes. In: Matrix vesicles. Proceedings of the Third International Conference on Matrix Vesicles. Mondeluco, Spoleto, pp 41–45
Holdsworth G, Coleman R (1976) Plasma membrane components can be removed from isolated lymphocytes by the bile salts glycocholate and taurocholate without cell lysis. Biochem J 158:493–495
Huggins JW, Trenbeath TP, Yeitman DR, Carraway KL (1980) Restricted concanavalin A redistribution on the branched microvilli of an ascites tumor subline. Exp Cell Res 127:31–46
Jacobs LR (1981) Alterations in surface ultrastructure and anionic sites of rat dimethylhydrazine-induced intestinal tumors. Virchows Arch [Cell Pathol] 37:207–216
Kim KM (1976) Calcification of matrix vesicles in human aortic valve and aortic media. Fed Proc 35:156–162
Koch GLE, Smith MJ (1978) An association between actin and the major histocompatibility antigen H-2. Nature 273:274–278
Krishan A, Frei E (1975) Morphological basis for the cytolytic effect of vinblastine and vincristine on cultured human leukemic lymphoblasts. Cancer Res 35:497–501
LeBlond CP (1972) Growth and renewal. In: Goss RJ (ed) Regulation of organ and tissue growth. Academic Press, New York, pp 13–39
Liepins A, Hillman AJ (1981) Shedding of tumor cell surface membranes. Cell Biol Int Rep 5:15–25
Liepins A, Faanes RB, Choi YS, de Harven E (1978) T-lymphocyte mediated lysis of tumor cells in the presence of alloantiserum. Cell Immunol 36:331–344
Lipper S, Dalzell JC, Watkins PJ (1979) Ultrastructure of psammoma bodies of meningioma in tissue culture. Arch Pathol Lab Med 103:670–675
Lutz HU, Liu S-C, Palek J (1977) Release of spectrin-free vesicles from human erythrocytes during ATP depletion. J Cell Biol 73:548–560
Marcus PI (1962) Dynamics of surface modification in myxovirusinfected cells. Cold Spring Harbor Symp on Quant Biol 27:351–365
Misch DW, Giebel PE, Faust RG (1980) Intestinal microvilli: responses to feeding and fasting. Eur J Cell Biol 21:269–279
Nguyen HT, Woodard JC (1980) Intranephronic calculosis in rats. Am J Pathol 100:39–56
Nowotny A, Grohsman J, Abdelnoor A, Rote N, Yang C, Watters-dorff R (1974) Escape of TA3-tumors from allogenic immune rejection: theory and experiments. Eur J Immunol 4:73–78
Nunez EA, Wallis J, Gershon MD (1974) Secretory processes in follicular cells of the bat thyroid. III. The occurrence of extracellular vesicles and colloid droplets during arousal from hibernation. Am J Anat 141:179–202
Ott P, Hope MJ, Verkleij AJ, Roelofsen B, Brodbeck U, Van Deenen LLM (1981) Effect of dimyristoyl phosphatidylcholine on intact erythrocytes. Release of spectrin-free vesicles without ATP depletion. Biochim Biophys Acta 641:79–87
Petitu M, Tuy F, Rosenfeld C, Mishal Z, Paintrand M, Jasnin C, Mathe G, Inbar M (1978) Decreased microviscosity of membrane lipids in leukemic cells: two possible mechanisms. Proc Natl Acad Sci USA 75:2306–2310
Poskitt PKF, Poskitt TR, Wallace JH (1976) Release into culture medium of membrane-associated tumor-specific antigen by B-16 melanoma cells (39332). Proc Soc Exp Biol Med 152:76–80
Rabinovitch AL, Anderson HC (1976) Biogenesis of matrix vesicles in cartilage growth plates. Fed Proc 35:112–116
Raz A, Goldman R, Yuli I, Inbar M (1978a) Isolation of plasma membrane fragments and vesicles from ascites fluid of lymphoma-bearing mice and their possible role in the escape mechanism of tumors from host immune rejection. Cancer Immunol Immunother 4:53–59
Raz A, Barzilai R, Spira G, Inbar M (1978b) Oncogenicity and immunogenicity associated with membranes isolated from cellfree ascites fluid of lymphoma-bearing mice. Cancer Res 38:2480–2485
Reed CF, Swisher SN (1966) Erythrocyte lipid loss in hereditary spherocytosis. J Clin Invest 45:777–781
Rittenhouse HG, Rittenhouse JW, Takemoto L (1978) Characterization of the cell coat of Ehrlich ascites tumor cells. Biochemistry 17:829–837
Roozemond RC, Urli DC (1981) Fluorescence polarization studies and biological properties of membranes exfoliated from the cell surface of rabbit thymocytes in situ. Biochim Biophys Acta 643:327–338
Sachs DH, Kiszkiss P, Kim KJ (1980) Release of la-antigens by a cultured B cell line. J Immunol 124:2130–2136
Scott RE (1976) Plasma membrane vesiculation: A new technique for isolation of plasma membrane. Science 194:743–745
Shapiro IM, Burke A, Schattschneider S, Golub EE (1981) Vesiculation of chondrocytes in vitro: a new technique for isolating vesicles from chondrocytes. In: Matrix vesicles. Proceedings of the Third International Conference on Matrix Vesicles, Monteluco, Spoleto, pp 33–39
Skinnider LF, Ghadially FN (1977) Ultrastructure of cell surface abnormalities in neoplastic histiocytes. Br J Cancer 35:657–667
Stanbridge EJ, Weiss RL (1978) Mycoplasma capping on lymphocytes. Nature 276:583–587
Tachiwaki O, Wollman SH (1982) Shedding of dense cell fragments into the follicular lumen early in involution of the hyperplastic thyroid gland. Lab Invest 47:91–98
Takeuchi A, Phillips BP (1976) Electron microscope studies of experimental Entamoeba histolytica infection in the guinea pig. Virchows Arch B [Cell Path] 20:1–13
Tanimura A, McGregor DH, Anderson HC (1983) Matrix vesicles in atherosclerotic calcification. Proc Soc Exp Biol Med 172:173–177
Trams EG, Lauter CJ, Salem N, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645:63–70
Van Blitterswijk WJ, Emmelot P, Hilkmann HAM, Oomen-Meulemans EPM, Inbar M (1977) Differences in lipid fluidity among isolated plasma membranes of normal and leukemic lymphocytes and membranes exfoliated from their surfaces. Biochim Biophys Acta 467:309–320
Van Blitterswijk WJ, Emmelot P, Hilkmann HAM, Hilgers J, Feltkamp CA (1979) Rigid plasma membrane-derived vesicles, enriched in tumour-associated surface antigens (MLr), occurring in the ascites fluid of a murine leukaemia (GRSL). Int J Cancer 23:62–70
Vitetta ES, Uhr JW (1972) Cell surface immunoglobulin. V. Release from murine splenic lymphocytes. J Exp Med 136:676–696
Vitetta ES, Uhr JW, Boyse EA (1974) Metabolism of H-2 and Thy-1 alloantigens in murine thymocytes. Eur J Immunol 4:276–282
Warshawsky H, Haddad A, Gonçalves RP, Vareri V, DeLucca FL (1973) Fine structure of the venom gland epithelium of the South American rattlesnake and radioautographic studies of protein formation by the secretory cells. Am J Anat 138:79–120
Weed RI, Bowdler AJ (1966) Metabolic dependence of the critical hemolytic volume of human erythrocytes: Relationship to osmotic fragility and autohemolysis in hereditary spherocytosis and normal red cells. J Clin Invest 7:1137–1149
Wollman SH, Breitman TR (1970) Changes in DNA and weight of thyroid glands during hyperplasia and involution. Endocrinology 86:322–327
Wollman SH, Loewenstein JE (1973) Rates of colloid droplet and apical vesicle production and membrane turnover during thyroglobulin secretion and resorption. Endocrinology 93:248–252
Young RW (1976) Visual cells and the concept of renewal. Invest Ophthalmol 15:700–725
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This study was supported by Grant No. 12X-537 from the Swedish Medical Research Council.
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Nilsson, M., Öfverholm, T. & Ericson, L.E. In vivo shedding of apical plasma membrane in the thyroid follicle cells of the mouse. Cell Tissue Res. 236, 87–97 (1984). https://doi.org/10.1007/BF00216517
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DOI: https://doi.org/10.1007/BF00216517