Effects of microparticle size and Fc density on macrophage phagocytosis

PLoS One. 2013 Apr 22;8(4):e60989. doi: 10.1371/journal.pone.0060989. Print 2013.

Abstract

Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm) is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism
  • Immunoglobulin Fc Fragments / chemistry*
  • Immunoglobulin Fc Fragments / metabolism
  • Macrophages / physiology*
  • Mice
  • Microspheres*
  • Opsonin Proteins / chemistry
  • Opsonin Proteins / metabolism
  • Particle Size
  • Phagocytosis*
  • Polystyrenes / chemistry
  • Polystyrenes / metabolism
  • Receptors, Fc / metabolism*

Substances

  • Drug Carriers
  • Immunoglobulin Fc Fragments
  • Opsonin Proteins
  • Polystyrenes
  • Receptors, Fc