Effects of Microparticle Size and Fc Density on Macrophage Phagocytosis

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.

Frustrated Phagocytic Spreading of J774A-1 Macrophages Ends in Myosin II-Dependent Contraction

“…Previous investigations of whether IgG opsonin density modulates the likelihood that a particle will be fully phagocytosed have yielded conflicting results (8,9). Additionally, how opsonin density affects phagocytic spreading rates has remained undocumented.…”

“…Despite the certainty that Fc-receptor binding drives actin protrusion, the dependence of phagocytic spreading rates on the bound receptor density has not yet been documented. Furthermore, there have been conflicting reports as to whether IgG opsonin density modulates the likelihood that a particle will be fully internalized (8,9). Theoretical models addressing endocytosis (particle internalization not necessarily requiring actin activity) posit that particle internalization rates depend on the ligand density (10)(11)(12).…”

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

“…Microparticles have been considered adequate for this end, ensuring not only the protection of the drugs until they reach the site of action, but also providing the necessary aerodynamic characteristics. To reach the alveoli, the aerodynamic diameter should be within 1-3 μm [5], but macrophage uptake is reported to be maximal for particles of 1-2 μm [6,7], thus identifying this size as a target in formulation design. Spray-drying has revealed appropriate to produce polymeric microparticles for inhalation purposes, being a versatile technique that permits tailoring microparticles to the desired characteristics, i.e., size, density and morphology [8].…”

Macrophage Uptake of Janus Particles Depends upon Janus Balance

“…18,27,28 For particles smaller than 2 µm, but not in other size ranges, their internalization efficiency increases with ligand density. 8 Shape matters too. For non-spherical particles, initiation of phagocytosis is determined by the local shape of the particle at its contact point with the cell.…”