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A polarized human endometrial cell line that binds and transports polymeric IgA

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Summary

We have demonstrated that a human endometrial cell line, HEC-1, maintains a high transepithelial electrical resistance, directionally transports fluids across the cell monolayer, and releases enveloped viruses at distinct plasma membrane domains: influenza virus is released at the apical surfaces and vesicular stomatitis virus (VSV) at the basolateral surfaces. In addition, we have examined the expression of domain-specific endogenous proteins, including the polyimmunoglobulin receptor. Multiple endogenous polypeptides were found to be secreted into the culture medium at basolateral surfaces, whereas no secretion of specific polypeptides was observed from apical cell surfaces. Distinct patterns of endogenous proteins were also observed on apical and basolateral cell surfaces, with a much more complex polypeptide pattern on the basolateral membranes. Using surface biotinylation and immunofluorescence, the polyimmunoglobulin receptor was found to be expressed on the basolateral surfaces of HEC-1 monolayers. The specific binding of poly-immunoglobulin A (pIgA) was found to occur on the basolateral surface, and was followed by transcytosis to the apical surface and release into the apical medium. The observed characteristics indicate that the endometrium-derived HEC-1 epithelial cell line can be employed as a model for studies of protein transport in polarized epithelial cells of human endometrial tissues, as well as for studies of the interaction of microorganisms with epithelial cells in the genital tract.

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References

  • Almers, W.; Stirling, C. Distribution of transport proteins over animal cell membranes. J. Membr. Biol. 77:169–186; 1984.

    Article  PubMed  CAS  Google Scholar 

  • Balcarova-Stander, J.; Pfeiffer, S. E.; Fuller, S. D., et al. Development of cell surface polarity in the epithelial Madin-Darby canine kidney (MDCK) cell line. EMBO J. 11:2687–2694; 1984.

    Google Scholar 

  • Bartles, J. R.; Hubbard, A. L. Plasma membrane protein sorting in epithelial cells: Do secretory proteins hold the key? Trends Biochem. Sci. 13:181–184; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Belec, L.; Georges, A. J.; Steenman, G., et al. Antibodies to human immunodeficiency virus in vaginal secretions of heterosexual women. J. Infect. Dis. 160:385–391; 1989a.

    PubMed  CAS  Google Scholar 

  • Belec, L.; Peghini, M.; Georges, A. J., et al. Antibodies to HIV-2 in genital secretions. Res. Virol. 140:15–21;1989b.

    Article  PubMed  CAS  Google Scholar 

  • Birkenfeld, A.; Ezra, Y.; Ron, N., et al. Indication of selective growth of human endometrial epithelial cells on extracellular matrix. In Vitro Cell. Dev. Biol. 12:1188–1192; 1988.

    Article  Google Scholar 

  • Bok, D.; O’Day, W.; Rodriguez-Boulan, E. Polarized budding of vesicular stomatitis and influenza virus from cultured human and bovine retinal pigment epithelium. Exp. Eye Res. 55:853–860; 1992.

    Article  PubMed  CAS  Google Scholar 

  • Brandtzaeg, P. Role of J chain and secretory component in receptor-mediated glandular and hepatic transport of immunoglobulins in man. Scand. J. Immunol. 22:111–146; 1985.

    Article  PubMed  CAS  Google Scholar 

  • Caplan, M.; Matlin, K. S. Sorting of membrane and secretory proteins in polarized epithelial cells. In: Matlin, K. S.; Valentich, J. D. eds. Functional epithelial cells in culture. New York: Liss; 1989:71–130.

    Google Scholar 

  • Cereijido, M.; Robbins, E. S.; Dolan, W. J., et al. Polarized monolayers formed by epithelial cells on a permeable and translucent support. J. Cell Biol. 77:853–880; 1978.

    Article  PubMed  CAS  Google Scholar 

  • Cereijido, M.; Stefani, E.; Martinez-Palomo, A. M. Occluding junctions in a cultured transporting epithelium: structural and functional heterogeneity. J. Membr. Biol. 53:19–32; 1980.

    Article  PubMed  CAS  Google Scholar 

  • Cooke, P. S.; Uchima, F.-D. A.; Fujii, D. K., et al. Restoration of normal morphology and estrogen responsiveness in cultured vaginal and uterine epithelial transplanted with stroma. Proc. Natl. Acad. Sci. USA 83:2109–2113; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Crickard, K.; Niedbala, M. J.; Crickard, U., et al. Characterization of human ovarian and endometrial carcinoma cell lines established on extracellular matrix. Gynecol. Oncol. 32:163–173; 1989.

    Article  PubMed  CAS  Google Scholar 

  • Diamond, J. M. The epithelial junction: bridge, gate, and fence. Physiologist 20:10–18; 1977.

    PubMed  CAS  Google Scholar 

  • Dimmock, N. J. Multiple mechanisms of neutralization of animal viruses. Trends Biochem. Sci. 12:70–75; 1987.

    Article  CAS  Google Scholar 

  • Finlay, B. B.; Falkow, S. Salmonella interactions with polarized human Caco-2 epithelial cells. J. Infect. Dis. 162:1096–1106; 1990.

    PubMed  CAS  Google Scholar 

  • Fuller, S. D.; Bonsdorff, C. H.; Simons, K. Vesicular stomatitus virus infects and matures only through the basolateral surface of the polarized epithelial cell line, MDCK. Cell 38:65–77; 1984.

    Article  CAS  Google Scholar 

  • Gottardi, C. J.; Caplan, M. J. Delivery of Na+, K+-ATPase in polarized epithelial cells. Science 260:552–554; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Gottlieb, T. A.; Beaudry, G.; Rizzolo, L., et al. Secretion of endogenous and exogenous proteins from polarized MDCK cell monolayers. Proc. Natl. Acad. Sci. USA 83:2100–2104; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Greenwood, F. C.; Hunter, W. M.; Glove, J. S. The preparation of131I-labeled growth hormone of high specific activity. Biochem. J. 89:114–123; 1963.

    PubMed  CAS  Google Scholar 

  • Gstraunthaler, G. J. A. Epithelial cells in tissue culture. Renal Physiol. Biochem. 11:1–42; 1988.

    PubMed  CAS  Google Scholar 

  • Haneberg, B.; Kendall, D.; Amerongen, H. M., et al. Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces. Infect. Immun. 62:15–23; 1994.

    PubMed  CAS  Google Scholar 

  • Hoppe, C. A.; Connolly, T. P.; Hubbard, A. L. Transcellular transport of polymeric IgA in the rat hepatocyte: biochemical and morphological characterization of the transport pathway. J. Cell Biol. 101:2113–2123; 1985.

    Article  PubMed  CAS  Google Scholar 

  • Hull, R. N.; Cherry, W. R.; Weaver, G. W. The origin and characteristics of a pig kidney cell strain LLC-PK1. In Vitro Cell. Dev. Biol. 12:670–677; 1976.

    Article  CAS  Google Scholar 

  • Jones, L. V.; Compans, R. W.; Davis, A. R., et al. Surface expression of the influenza neuraminidase, an amino-terminally anchored viral membrane glycoprotein, in polarized epithelial cells. Mol. Cell. Biol. 5:2181–2189; 1985.

    PubMed  CAS  Google Scholar 

  • Kraehenbuhl, J. P.; Neutra, M. R. Monoclonal secretory IgA for protection of the intestinal mucosa against viral and bacterial pathogens. In: Ogra, P. L.; Mestecky, J.; Lamm, M. E., et al., eds. Handbook of mucosal immunology. San Diego: Academic Press; 1994:403–410.

    Google Scholar 

  • Kuramoto, H.; Tamura, S.; Yukio, N. Establishment of a cell line of human endometrial adenocarcinoma in vitro. Am. J. Obstet. Gynecol. 114:1012–1019; 1972.

    PubMed  CAS  Google Scholar 

  • Kutteh, W. H.; Edwards, R. P.; Menge, A. C., et al. IgA immunity in female reproductive tract secretions. In: Griffin, P. D.; Johnson, P. M., eds. Local immunity in reproductive tract tissues. Oxford: Oxford University Press; 1993:17–51.

    Google Scholar 

  • Leighton, J.; Brada, Z.; Estes, L. W., et al. Secretory activity and oncogenicity of a cell line (MDCK) derived from canine kidney. Science 163:472–473; 1969.

    Article  PubMed  CAS  Google Scholar 

  • Marx, P. A.; Compans, R. W.; Gettie, A., et al. Protection against SIV vaginal transmission with microencapsulated vaccine. Science: 260:1323–1327; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Mazanec, M. B.; Kaetzel, C. S.; Lamm, M. E., et al. Intracellular neutralization of virus by immunoglobulin A antibodies. Proc. Natl. Acad. Sci. USA 89:6901–6905; 1992.

    Article  PubMed  CAS  Google Scholar 

  • McGarrity, G. J.; Steiner, T.; Vanaman, V. Detection of mycoplasmal infection of cell cultures by DNA fluorochrome staining. In: Tully, J. G.; Razin, S., eds. Methods in mycoplasmology, vol. II. 1983:183–190.

    Google Scholar 

  • Menge, A. C.; Mestecky, J. Surface expression of secretory component and HLA class II DR antigen on glandular epithelial cells from human endometrium and two endometrial adenocarcinoma cell lines. J. Clin. Immunol. 13:1–5; 1993.

    Article  Google Scholar 

  • Mestecky, J.; Kilian, M. Immunoglobulin A (IgA). Methods Enzymol. 116:37–75; 1985.

    PubMed  CAS  Google Scholar 

  • Mestecky, J.; Lue, C.; Russell, M. W. Selective transport of IgA, cellular and molecular aspects. Gastroenterol. Clin. North Am. 20:441–471; 1991.

    PubMed  CAS  Google Scholar 

  • Mestecky, J.; McGhee, J. R. Immunoglobulin A (IgA): Molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv. Immunol. 40:153–245; 1987.

    Article  PubMed  CAS  Google Scholar 

  • Misfeldt, D. S.; Hamamoto, S. T.; Pitelka, D. R. Transepithelial transport in cell culture. Proc. Natl. Acad. Sci. USA 73:1212–1216; 1976.

    Article  PubMed  CAS  Google Scholar 

  • Mostov, K. E.; Deitcher, D. L. Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell 46:613–621; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Mostov, K. E.; Simister, N. E. Transcytosis. Cell 43:388–390; 1985.

    Article  Google Scholar 

  • Nagura, H.; Nakane, P. K.; Brown, W. R. Translocation of dimeric IgA through neoplastic colon cells in vitro. J. Immunol. 123:2359–2368; 1979.

    PubMed  CAS  Google Scholar 

  • Nitsch, L.; Tramontano, D.; Ambesi-Impiombato, F. S., et al. Morphological and functional polarity in an epithelial thyroid cell line. Eur. J. Cell. Biol. 38:57–66; 1985.

    PubMed  CAS  Google Scholar 

  • Noumoff, J.; Haydock, S. W.; Sachdeva, R., et al. Characteristics of cell lines derived from normal and malignant endometrial tissue. Gynecol. Oncol. 27:141–149; 1987.

    Article  PubMed  CAS  Google Scholar 

  • Ogra, P. L.; Ogra, S. S. Local antibody response to polio vaccine in the human female genital tract. J. Immunol. 110:1307–1312; 1973.

    PubMed  CAS  Google Scholar 

  • O’Shea, S.; Cordey, M.; Barrett, W. Y., et al. HIV excretion patterns and specific antibody responses in body fluids. J. Med. Virol. 31:291–296; 1990.

    Article  PubMed  CAS  Google Scholar 

  • Owens, R. J.; Dubay, J.; Hunter, E., et al. The human immunodeficiency virus envelope protein determines the site of virus release in polarized epithelial cells. Proc. Natl. Acad. Sci. USA 88:3987–3991; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Rhinehart, C.A., Jr.; Lyn-Cook, B. D.; Kaufman, D. G. Gland formation from human endometrial epithelial cells in vitro. In Vitro Cell. Dev. Biol. 24:1037–1041; 1988.

    Article  Google Scholar 

  • Richardson, G. S.; Dickersin, G. R.; Atkins, L., et al. KLE: A cell line with defective estrogen receptor derived from undifferentiated endometrial cancer. Gynecol. Oncol. 17:213–230; 1984.

    Article  PubMed  CAS  Google Scholar 

  • Rindler, M. J.; Traber, M. G. A specific sorting signal is not required for the polarized secretion of newly synthesized proteins from cultured intestinal epithelial cells. J. Cell Biol. 107:471–479; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Boulan, E.; Powell, S. K. Polarity of epithelial and neuronal cells. Annu. Rev. Cell Biol. 8:395–427; 1992.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Boulan, E.; Sabatini, D. D. Morphogenesis of the polarized epithelial phenotype. Proc. Natl. Acad. Sci. USA 75:5071–5075; 1978.

    Article  CAS  PubMed  Google Scholar 

  • Roth, M. G.; Compans, R. W.; Giusti, L., et al. Influenza virus hemagglutinin expression is polarized in cells infected with recombinant SV40 viruses carrying cloned hemagglutinin DNA. Cell 33:435–442; 1983a.

    Article  PubMed  CAS  Google Scholar 

  • Roth, M. G.; Srinivas, R. V.; Compans, R. W. Basolateral maturation of retroviruses in polarized epithelial cells. J. Virol. 45:1065–1073; 1983b.

    PubMed  CAS  Google Scholar 

  • Roth, M. G.; Fitzpatrick, J. P.; Compans, R. W. Polarity of influenza and vesicular stomatitis virus maturation in MDCK cells: lack of a requirement for glycosylation of viral glycoproteins. Proc. Natl. Acad. Sci. USA 76:6430–6434; 1979.

    Article  PubMed  CAS  Google Scholar 

  • Sargiacomo, M.; Lisanti, M.; Graeve, L., et al. Integral and peripheral protein composition of the apical and basolateral membrane domains in MDCK cells. Membr. Biol. 107:277–286; 1989.

    Article  CAS  Google Scholar 

  • Schaerer, E.; Verrey, F.; Racine, L., et al. Polarized transport of the polymeric immunoglobulin receptor in transfected rabbit mammary epithelial cells. J. Cell Biol. 110:987–998; 1990.

    Article  PubMed  CAS  Google Scholar 

  • Simons, K.; van Meer, G. Lipid sorting in epithelial cells. Biochemistry 27:6197–6202; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Simons, K.; Wandinger-Ness, A. Polarized sorting in epithelia. Cell 62:207–210; 1990.

    Article  PubMed  CAS  Google Scholar 

  • Spies, C. P.; Ritter, G. D., Jr.; Mulligan, M. J., et al. Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters conformation of the external domain. J. Virol. 68:585–591; 1994.

    PubMed  CAS  Google Scholar 

  • Stephens, E. B.; Compans, R. W.; Earl, P., et al. Surface expression of viral glycoproteins in polarized epithelial cells using vaccinia virus vectors. EMBO J. 5:237–245; 1986.

    PubMed  CAS  Google Scholar 

  • Taub, M. Tissue culture of epithelial cells. New York: Plenum Press; 1985.

    Google Scholar 

  • Tobita, K.; Sugiura, A.; Enomoto, C., et al. Plaque assay and primary isolation of influenza A viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin. Med. Microbiol. Immunol. 162:9–14; 1975.

    Article  PubMed  CAS  Google Scholar 

  • Trent, J. M.; Davis, J. R.; Payne, C. M. The establishment and morphologic characterization of finite cell lines from normal human endometrium. Am. J. Obstet. Gynecol. 136:352–362; 1980.

    PubMed  CAS  Google Scholar 

  • Tucker, S. P.; Compans, R. W. Virus infection of polarized epithelial cells. In: Maramorosch, K.; Murphy, F. A.; Shatkin, A. J., eds. Advances in virus research. Vol. 42. Academic Press: 1993:187–247.

  • Underdown, B. J.; Schiff, J. M. Immunoglobulin A: strategic defense initiative at the mucosal surface. Annu. Rev. Immunol. 4:389–417; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Urban, J.; Parczyk, K.; Leutz, A., et al. Constitutive apical secretion of an 80-kD sulfated glycoprotein complex in the polarized epithelial Madin-Darby canine kidney cell line. J. Cell Biol. 105:2735–2743; 1987.

    Article  PubMed  CAS  Google Scholar 

  • Wira, Charles R. Endocrine regulation of mucosal immunity: effect of sex hormones and cytokines on the afferent and efferent arms of the immune system in the female reproductive tract. In: Ogra, P. L.; Mestecky, J.; Lamm, M. E., eds. Handbook of mucosal immunology. San Diego: Academic Press; 1994:705–718.

    Google Scholar 

  • Wollner, K.; Krzeminski, K.; Nelson, J. Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity. J. Cell Biol. 116:889–899; 1992.

    Article  PubMed  CAS  Google Scholar 

  • Zurzolo, C.; Le Bivic, A.; Quaroni, A., et al. Modulation of transcytotic and direct targeting pathways in a polarized thyroid cell line. EMBO J. 11:2337–2344; 1992.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, University of Alabama at Birmingham, 35294, Birmingham, Alabama

    Judith M. Ball, Zina Moldoveanu, Pamela A. Kozlowski, Susan Jackson, Mark J. Mulligan & Jiri F. Mestecky

  2. Department of Microbiology and Immunology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road Atlanta, 30322, Georgia

    Lawrence R. Melsen & Richard W. Compans

  3. Division of Infectious Diseases Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, Alabama

    Mark J. Mulligan

  4. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, Alabama

    Jiri F. Mestecky

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  1. Judith M. Ball
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  2. Zina Moldoveanu
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  3. Lawrence R. Melsen
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  7. Jiri F. Mestecky
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Ball, J.M., Moldoveanu, Z., Melsen, L.R. et al. A polarized human endometrial cell line that binds and transports polymeric IgA. In Vitro Cell Dev Biol - Animal 31, 196–206 (1995). https://doi.org/10.1007/BF02639434

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