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Phagocytotic Competence of Differentiated U937 Cells for Colloidal Drug Delivery Systems in Immune Cells

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Abstract

Drug delivery into immune cells has high potential for the treatment of all kinds of inflammation, allowing a target-oriented transport of active agents. The advantage of this local drug release is the prevention of negative effects of systemic applications and low-dose application. Thereby, the phagocytotic capability of mature phagocytes is essential. Microparticles can be loaded with immune regulatory substances to control and terminate inflammatory processes. In this study, silica microparticles were co-incubated with monocyte/macrophage-like cells in order to determine phagocytotic particle uptake. The phorbol ester-triggered differentiation was proven by the increased expression of surface markers as phosphatidylserine and CD14 and enhanced lysosomal activity. Particle/cell co-incubation results in cell surface attachment followed by phagocytosis. Phagolysosomal ingestion could be determined by co-localization using fluorescence staining techniques. In contrast, no particle interaction with undifferentiated cells could be found. Under phagolysosomal conditions, multilayer degradation within 22 h could be shown, indicating a valuable carrier basis design for the time-controlled delivery of active agents. Subsequently, it can be assumed that a higher differentiation degree allows phagocytosis of microparticles, providing drug delivery into immuno-active cells.

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References

  1. Libby, P. 2008. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. American Journal of Medicine 121(Suppl 1): S21–S31.

    Article  PubMed  CAS  Google Scholar 

  2. Dubertret, L. 2009. Retinoids, methotrexate and cyclosporine. Current Problems in Dermatology 38: 79–94.

    Article  PubMed  Google Scholar 

  3. Adamson, R. 2009. Role of macrophages in normal wound healing: An overview. Journal of Wound Care 18: 349–351.

    PubMed  CAS  Google Scholar 

  4. Vieira, O.V., R.J. Botelho, and S. Grinstein. 2002. Phagosome maturation: Aging gracefully. The Biochemical Journal 366: 689–704.

    PubMed  CAS  Google Scholar 

  5. Reibetanz, U., C. Claus, E. Typlt, J. Hofmann, and E. Donath. 2006. Defoliation and plasmid delivery with layer-by-layer coated colloids. Macromolecular Biosciences 6: 153–160.

    Article  CAS  Google Scholar 

  6. Metz, T., T. Haque, H. Chen, and S. Prakash. 2006. Preparation and in vitro analysis of microcapsule thalidomide formulation for targeted supression of TNF-α. Drug Delivery 13: 331–337.

    Article  PubMed  CAS  Google Scholar 

  7. Kakade, S., D.S. Manickam, H. Handa, G. Mao, and D. Oupicky. 2009. Transfection activity of layer-by-layer plasmid DNA/poly(ethylenimine) films deposited on PLGA microparticles. International Journal of Pharmaceutics 365: 44–52.

    Article  PubMed  CAS  Google Scholar 

  8. Matsumoto, K., M. Terakawa, S. Fukuda, and H. Saito. 2007. Rapid and strong induction of apoptosis in human eosinophils by anti-cd30 mAB-coated microspheres and phagocytosis by macrophages. International Archives of Allergy and Immunology 143(suppl 1): 60–67.

    Article  PubMed  Google Scholar 

  9. Cortez, C., E. Tomaskovic-Crook, A.P.R. Johnston, A.M. Scott, E.C. Nice, J.K. Heath, and F. Caruso. 2007. Influence of size, surface, cell line, and kinetic properties on the specific binding of A33 antigen-targeted multilayered particles and capsules to colorectal cancer cells. American Chemical Society Nano 1: 93–102.

    PubMed  CAS  Google Scholar 

  10. Sundstrom, C., and K. Nilsson. 1976. Establishment and characterization of a human histiocytic lymphoma cell line (U937). International Journal of Cancer 17: 565–577.

    Article  CAS  Google Scholar 

  11. Larrick, J.W., D.G. Fischer, S.J. Anderson, and H.S. Koren. 1980. Characterization of human macrophage-like cell line stimulated in vitro: A model of macrophage functions. Journal of Immunology 125: 6–12.

    CAS  Google Scholar 

  12. Callahan, M.K., M.S. Halleck, S. Krahling, A.J. Henderson, P. Williamson, and R.A. Schlegel. 2003. Phosphatidylserine expression and phagocytosis of apoptotic thymocytes during differentiation of monocytic cells. Journal of Leukocyte Biology 74: 846–856.

    Article  PubMed  CAS  Google Scholar 

  13. Callahan, M.K., P. Williamson, and R.A. Schlegel. 2000. Surface expression of phosphatidylserine on macrophages is required for phagocytosis of aptotic thymocytes. Cell Death and Differentiation 7: 645–653.

    Article  PubMed  CAS  Google Scholar 

  14. Williamson, P., and R.A. Schlegel. 2002. Transbilayer phospholipid movement and the clearance of apoptotic cells. Biochimica et Biophysica Acta 1585: 53–63.

    PubMed  CAS  Google Scholar 

  15. Alessio, M., L. De Monte, A. Scirea, P. Gruarin, N.N. Tandon, and R. Sitia. 1996. Synthesis, processing and intracellular transport of CD36 during monocytic differentiation. The Journal of Biological Chemistry 271: 1770–1775.

    Article  PubMed  CAS  Google Scholar 

  16. Kaul, M., and M. Loos. 1995. Collagen-like complement component C1q is a membrane protein of human monocyte-derived macrophages that mediates endocytosis. Journal of Immunology 155: 5795–5802.

    CAS  Google Scholar 

  17. Spittler, A., M. Willheim, F. Leutmezer, R. Öhler, W. Krugluger, C. Reissner, T. Lucas, T. Brodowicz, E. Roth, and G. Boltz-Nitulescu. 1997. Effects of 1α, 25-dihydroxyvitamin D3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: Role in cell differentiation, activation and phagocytosis. Immunology 90: 286–293.

    Article  PubMed  CAS  Google Scholar 

  18. Pagliara, P., R. Lanubile, M. Dwikat, L. Abbro, and L. Dini. 2005. Differentiation of monocytic U937 cells under static magnetic field exposure. European Journal of Histochemistry 49: 75–86.

    PubMed  CAS  Google Scholar 

  19. Glander, H.J., and J. Schaller. 1999. Binding of annexin V to plasma membranes of human spermatozoa: A rapid assay for detection of membrane changes after cryostorage. Molecular Human Reproduction 5: 109–115.

    Article  PubMed  CAS  Google Scholar 

  20. Traganos, F., and Z. Darzynkiewicz. 1994. Lysosomal proton pump activity: Supravital cell staining with acridine orange differentiates leukocyte subpopulations. Methods in Cell Biology 41: 421–435.

    Article  PubMed  Google Scholar 

  21. Liao, Y.F., H.C. Hung, P.C. Hsu, M.C. Kao, T.C. Hour, G.J. Tsay, and G.Y. Liu. 2008. Ornithine decarboxylase interferes with macrophage-like differentiation and matrix metalloproteinase-9 expression by tumor necrosis factor alpha via NF-κB. Leukemia Research 32: 1124–1140.

    Article  PubMed  CAS  Google Scholar 

  22. Kielian, M.C., and Z.A. Cohn. 1981. Phorbol myristate acetate stimulates phagosome–lysosome fusion in mouse macrophages. The Journal of Experimental Medicine 154: 101–111.

    Article  PubMed  CAS  Google Scholar 

  23. Decher, G. 1997. Fuzzy nanoassemblies: Toward layered polymeric multicomposites. Science 277: 1232–1237.

    Article  CAS  Google Scholar 

  24. Kunkel, S.L., and R.E. Duque. 1983. The macrophage adherence phenomenon: Its relationship to prostaglandin E2 and superoxide anion production and changes in the transmembrane potential. Prostaglandins 26: 893–904.

    Article  PubMed  CAS  Google Scholar 

  25. Greenberger, J.S., P.E. Newburger, and M. Sakakeeny. 1980. Phorbol myristate acetate stimulates macrophage differentiation and replication and alters granulopoiesis and leukemogenesis in long-term bone marrow cultures. Blood 56: 368–379.

    PubMed  CAS  Google Scholar 

  26. Todd 3rd, R.F., J.D. Griffin, J. Ritz, L.M. Nadler, T. Abrams, and S.F. Schlossman. 1981. Expression of normal monocyte-macrophage differentiation antigens on HL-60 promyelocytes undergoing differentiation induced by leukocyte-conditioned medium or phorbol diester. Leukemia Research 5: 491–495.

    Article  PubMed  Google Scholar 

  27. Melamed, M.R., L.R. Adams, F. Traganos, A. Zimring, and L.A. Kamentsky. 1972. Acridine orange metachromasia for characterization of leukocytes in leukemia, lymphoma, and other neoplasms. Cancer 29: 1361–1368.

    Article  PubMed  CAS  Google Scholar 

  28. Melamed, M.R., L.R. Adams, F. Traganos, and L.A. Kamentsky. 1974. Blood granulocyte staining with acridine orange. Changes with infection. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society 22: 526–530.

    CAS  Google Scholar 

  29. Krahling, S., M.K. Callahan, P. Williamson, and R.A. Schlegel. 1999. Exposure of phosphatidylserine is a general feature in the phagocytosis of apoptotic lymphocytes by macrophages. Cell Death and Differentiation 6: 183–189.

    Article  PubMed  CAS  Google Scholar 

  30. Jiang, Q., S. Akashi, K. Miyake, and H. Petty. 2000. Lipopolysaccharide induces physical proximity between CD14 and Toll-like receptor 4 (TLR4) prior to nuclear translocation of NFκB. Journal of Immunology 165: 3541–3544.

    CAS  Google Scholar 

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Acknowledgments

The work presented in this paper was made possible by funding from the German Federal Ministry of Education and Research (BMBF, PtJ-Bio, 0313909). Additionally, this work was supported by grants from the German Research Foundation (Project Gl 199/4-3) and the Ministry of Education (Singapore).

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Authors and Affiliations

  1. Institute of Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany

    Jacqueline Leßig, Jürgen Arnhold & Uta Reibetanz

  2. Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany

    Jacqueline Leßig & Uta Reibetanz

  3. School of Chemical and Biomedical Engineering, Division of Bioengineering, Nanyang Technological University, Singapore, Singapore

    Björn Neu

  4. Department of Dermatology/Andrological Training Centre of the European Academy of Andrology, Leipzig, Germany

    Hans-Jürgen Glander

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  1. Jacqueline Leßig
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  2. Björn Neu
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  3. Hans-Jürgen Glander
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  4. Jürgen Arnhold
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  5. Uta Reibetanz
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Correspondence to Jacqueline Leßig.

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Leßig, J., Neu, B., Glander, HJ. et al. Phagocytotic Competence of Differentiated U937 Cells for Colloidal Drug Delivery Systems in Immune Cells. Inflammation 34, 99–110 (2011). https://doi.org/10.1007/s10753-010-9213-4

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  • DOI: https://doi.org/10.1007/s10753-010-9213-4

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