Skip to main content
SpringerLink
Log in

Reaching the Macrophage: Routes of Delivery

  • Chapter
The Macrophage as Therapeutic Target

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 158))

  • 460 Accesses

Abstract

The functional heterogeneity of macrophages based on anatomical localization and receptor expression as well as their versatile way through which they react to different stimuli makes them key players in many processes of the body. To stimulate or downregulate their functions in therapeutic ways using their extremely efficient phagocytosis capacity, one has to consider that they are often located at sites that are hard to reach. Local administration of drugs is therefore often the method of choice whereby liposomes seem to be an ideal vehicle through their versatility and relative ease of handling, as well as their efficient uptake by macrophages. Especially the use of the macrophage suicide technique has enabled the study of many functions of the macrophage. An overview is given of the many routes that can be used to reach the macrophage at different sites and the effects this has on the function of the cell.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aderem A, Underhill DM (1999) Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17:593–623

    Article  PubMed  CAS  Google Scholar 

  • Barbe E, Huitinga I, Dopp EA, Bauer J, Dijkstra CD (1996) A novel bone marrow frozen section assay for studying hematopoietic interactions in situ: the role of stromal bone marrow macrophages in erythroblast binding. J Cell Sci 109:2937–2945

    PubMed  CAS  Google Scholar 

  • Barrera P, Blom A, van Lent PL, van Bloois L, Beijnen JH, van Rooijen N, de Waal Malefijt MC, et al (2000) Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis. Arthritis Rheum 43:1951–1959

    Article  PubMed  CAS  Google Scholar 

  • Bergh A, Damber JE, van Rooijen N (1993) The human chorionic gonadotrophin-induced inflammation-like response is enhanced in macrophage-depleted rat testes. J Endocrinol 136:415–420

    Article  PubMed  CAS  Google Scholar 

  • Biewenga J, van der Ende MB, Krist LF, Borst A, Ghufron M, van Rooijen N (1995) Macrophage depletion in the rat after intraperitoneal administration of liposome-encap-sulated clodronate: depletion kinetics and accelerated repopulation of peritoneal and omental macrophages by administration of Freund’s adjuvant. Cell Tissue Res 280:189–196

    PubMed  CAS  Google Scholar 

  • Carroll MC (1998) The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 16:545–568

    Article  PubMed  CAS  Google Scholar 

  • Delemarre FG, Kors N, Kraal G, van Rooijen N (1990) Repopulation of macrophages in popliteal lymph nodes of mice after liposome-mediated depletion. J Leukoc Biol 47:251–257

    PubMed  CAS  Google Scholar 

  • Fadok VA, Bratton DL, Henson PM (2001) Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences. Journal of Clinical Investigation 108:957–962

    PubMed  CAS  Google Scholar 

  • Fathi M, Johansson A, Lundborg M, Orre L, Skold CM, Camner P (2001) Functional and morphological differences between human alveolar and interstitial macrophages. Experimental and Molecular Pathology 70:77–82

    Article  PubMed  CAS  Google Scholar 

  • Gerber JS, Mosser DM (2001) Stimulatory and inhibitory signals originating from the macrophage Fc gamma receptors. Microbes and Infection 3:131–139

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis G (1995) Engineering liposomes for drug delivery: progress and problems. Trends Biotechnol 13:527–537

    Article  PubMed  CAS  Google Scholar 

  • Holt PG, Oliver J, Bilyk N, McMenamin C, McMenamin PG, Kraal G, Thepen T (1993) Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med 177:397–407

    Article  PubMed  CAS  Google Scholar 

  • Janeway CA Jr (1992) The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 13:11–16

    Article  PubMed  CAS  Google Scholar 

  • Kraal G (1992) Cells in the marginal zone of the spleen. Int Rev Cytol 132:31–74

    Article  PubMed  CAS  Google Scholar 

  • Krieger M, Herz J (1994) Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem 63:601–637

    Article  PubMed  CAS  Google Scholar 

  • Laskin DL, Weinberger B, Laskin JD (2001) Functional heterogeneity in liver and lung macrophages. Journal of Leukocyte Biology 70:163–170

    PubMed  CAS  Google Scholar 

  • Litzinger DC, Buiting AM, van Rooijen N, Huang L (1994) Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. Biochim Biophys Acta 1190:99–107

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R, Janeway C Jr (2000) The Toll receptor family and microbial recognition. Trends Microbiol 8:452–456

    Article  PubMed  CAS  Google Scholar 

  • Nolte M (2002) Compartments, cells and molecules in the spleen, Academic thesis. Vrije Universiteit medical center, Amsterdam

    Google Scholar 

  • Pantelidis P, McGrath DS, Southcott AM, Black CM, du Bois RM (2001) Tumour necrosis factor-alpha production in fibrosing alveolitis is macrophage subset specific. Respiratory Research 2:365–372

    Article  PubMed  CAS  Google Scholar 

  • Pearson AM (1996) Scavenger receptors in innate immunity. Curr Opin Immunol 8:20–28

    Article  PubMed  CAS  Google Scholar 

  • Peiser L, Mukhopadhyay S, Gordon S (2002) Scavenger receptors in innate immunity. Curr Opin Immunol 14:123–128

    Article  PubMed  CAS  Google Scholar 

  • Platt N, Gordon S (2001) Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse’s tale. Journal of Clinical Investigation 108:649–654

    PubMed  CAS  Google Scholar 

  • Platt N, Suzuki H, Kurihara Y, Kodama T, Gordon S (1996) Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proceedings of the National Academy of Sciences of the United States of America 93:12456–12460

    CAS  Google Scholar 

  • Polfliet MM, Goede PH, van Kesteren-Hendrikx EM, van Rooijen N, Dijkstra CD, van den Berg TK (2001) A method for the selective depletion of perivascular and meningeal macrophages in the central nervous system. J Neuroimmunol 116:188–195

    Article  PubMed  CAS  Google Scholar 

  • Rabinovitch M (1995) Professional and Nonprofessional Phagocytes - an Introduction. Trends in Cell Biology 5:85–87

    Article  PubMed  CAS  Google Scholar 

  • Ravetch JV (1997) Fc receptors. Curr Opin Immunol 9:121–125

    Article  PubMed  CAS  Google Scholar 

  • Ravetch JV, Clynes RA (1998) Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16:421–432

    Article  PubMed  CAS  Google Scholar 

  • Riches DWH (1995) Signaling Heterogeneity as a Contributing Factor in Macrophage Functional Diversity. Seminars in Cell Biology 6:377–384

    Article  PubMed  CAS  Google Scholar 

  • Savill J (1998) Apoptosis - Phagocytic docking without shocking. Nature 392:442–443

    Article  PubMed  CAS  Google Scholar 

  • Savill J, Fadok V, Henson P, Haslett C (1993) Phagocyte Recognition of Cells Undergoing Apoptosis. Immunology Today 14:131–136

    Article  PubMed  CAS  Google Scholar 

  • Schumann J, Wolf D, Pahl A, Brune K, Papadopoulos T, van Rooijen N, Tiegs G (2000) Importance of Kupffer cells for T-cell-dependent liver injury in mice. Am J Pathol 157:1671–1683

    Article  PubMed  CAS  Google Scholar 

  • Stahl PD, Ezekowitz RA (1998) The mannose receptor is a pattern recognition receptor involved in host defense. Curr Opin Immunol 10:50–55

    Article  PubMed  CAS  Google Scholar 

  • Stein M, Gordon S (1991) Regulation of Tumor-Necrosis-Factor (Tnf) Release by Murine Peritoneal-Macrophages - Role of Cell Stimulation and Specific Phagocytic Plasma-Membrane Receptors. European Journal of Immunology 21:431–437

    Article  PubMed  CAS  Google Scholar 

  • Takai T, Li M, Sylvestre D, Clynes R, Ravetch JV (1994) FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 76:519–529

    Article  PubMed  CAS  Google Scholar 

  • Thepen T, Van Rooijen N, Kraal G (1989) Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med 170:499–509

    Article  PubMed  CAS  Google Scholar 

  • Thepen T, van Vuuren AJ, Kiekens RC, Damen CA, Vooijs WC, van De Winkel JG (2000) Resolution of cutaneous inflammation after local elimination of macrophages. Nat Biotechnol 18:48–51

    Article  PubMed  CAS  Google Scholar 

  • van Rooijen N, Bakker J, Sanders A (1997) Transient suppression of macrophage functions by liposome-encapsulated drugs. Trends Biotechnol 15:178–185

    Article  PubMed  Google Scholar 

  • van Rooijen N, Claassen E, Kraal G, Dijkstra CD (1989a) Cytological basis of immune functions of the spleen. Immunocytochemical characterization of lymphoid and non-lymphoid cells involved in the ’in situ’ immune response. Prog Histochem Cyto-chem 19:1–71

    Google Scholar 

  • van Rooijen N, Kors N, Kraal G (1989b) Macrophage subset repopulation in the spleen: differential kinetics after liposome-mediated elimination. J Leukoc Biol 45:97–104

    PubMed  Google Scholar 

  • Van Rooijen N, Kors N, vd Ende M, Dijkstra CD (1990) Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate. Cell Tissue Res 260:215–222

    Article  PubMed  Google Scholar 

  • Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174:83–93

    Article  PubMed  Google Scholar 

  • van Rooijen N, Sanders A (1997) Elimination, blocking, and activation of macrophages: three of a kind? J Leukoc Biol 62:702–709

    PubMed  Google Scholar 

  • van Rooijen N, ter Hart H, Kraal G, Kors N, Claassen E (1992) Monoclonal antibody mediated targeting of enzymes. A comparative study using the mouse spleen as a model system. J Immunol Methods 151:149–155

    Article  PubMed  Google Scholar 

  • Wright SD, Silverstein SC (1983) Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J Exp Med 158:2016–2023

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    G. Kraal & N. van Rooijen

Authors
  1. G. Kraal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. van Rooijen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE, Oxford, UK

    Siamon Gordon

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kraal, G., van Rooijen, N. (2003). Reaching the Macrophage: Routes of Delivery. In: Gordon, S. (eds) The Macrophage as Therapeutic Target. Handbook of Experimental Pharmacology, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55742-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-55742-2_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62919-8

  • Online ISBN: 978-3-642-55742-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation