Abstract
BackgroundAntibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a size-dependent effect on clearance.Methodology/Principal FindingsWe used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal) and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1–2 micron) by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2–5 micron) and apoptotic microparticles (<2 µm) released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads.Conclusions/SignificanceTherefore, while the shape of the particles is important for non-opsonized particle uptake, the particle size matters for antibody-mediated clearance by macrophages. IgM particularly promotes the clearance of small size particles. This finding may have wider implications in IgM-mediated clearing of antigens, microbial pathogens and dying cells by the host.
Highlights
Particle clearance is an essential function performed by phagocytes such as macrophages [1]
We propose that IgM-opsonized small particle clearance is an alternative pathway to bypass the need for complement activating inflammation-exacerbating pathway that causes excessive tissue damage
To evaluate the ability of IgM to regulate the uptake of biological material, we used sheep red blood cells (sRBC) as a model biological particle (,7–10 mm) for phagocytosis [35]
Summary
Particle clearance is an essential function performed by phagocytes such as macrophages [1]. It is very well established that IgG-coated particles are engulfed efficiently by macrophages [4,5]; yet, little is known about the role of IgM in particle clearance. Recent studies indicate that shape, but not the size, is critical to the uptake of particles by macrophages [6]. The aim of this study is to determine the importance of particle size in IgM-opsonized particle clearance. The mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; the relevance of IgM and particle size in their clearance remains unclear. We show that IgM has a sizedependent effect on clearance
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