Abstract
CD200 is known as an anti-inflammatory transmembrane glycoprotein in the immunoglobulin superfamily. CD200 interacts with its receptor CD200R which is highly expressed on myeloid cells such as macrophages and neutrophils. CD200-CD200R interaction has known to reduce macrophage activation and chronic inflammation. To harness the immunomodulatory property of CD200 for surface modification, CD200-streptavidin fusion protein was expressed from bacteria transformed with pET20b plasmid encoded with CD200 extracellular domain and core streptavidin. The purified CD200-SA protein was bound to biotin-coated fluorescent polystyrene particles of various sizes ranging from 0.15 to 2 µm. THP-1 macrophages were cultivated with CD200-modified micro/nanoparticles in comparison with controls. Our results showed that both nano- and micro-sized particles decorated with CD200 decreased phagocytosis activities of THP-1 macrophages. Such diminution of phagocytosis was examined to be associated with downregulation of Toll-like receptor 4 (TLR4) expression on the surface of macrophages. Moreover, THP-1 macrophages treated with CD200-coated particles decreased the secretion of tumor necrosis factor-α (TNF-α).
Highlights
Macrophage is a phagocyte of the immune system that engulfs foreign microbes and cellular debris[1]
Our results showed that both nano- and micro-sized particles decorated with CD200 decreased phagocytosis activities of THP-1 macrophages
The gene sequences of hCD200 and core streptavidin (coreSA) from PMZ006 were amplified by polymerase chain reaction (PCR), and the PCR products were characterized by DNA gel electrophoresis (Fig. 1b)
Summary
Macrophage is a phagocyte of the immune system that engulfs foreign microbes and cellular debris[1]. CD200R known as CD200 cognate receptor is expressed on the surface myeloid cells such as macrophages, neutrophils, and microglia[13,14]. The surfaces of polystyrene particles with sizes ranging from nano- to micro-meters were coated with CD200 to evaluate the effect of CD200 on macrophage phagocytosis. We hypothesized that surface modification of micro/nanoparticles would decrease macrophage phagocytosis as well as the secretion of pro-inflammatory cytokines through CD200-CD200R interaction. Our results showed that both nano- and micro-sized particles decorated with CD200 decreased phagocytosis activities of THP-1 macrophages. Surface modification with CD200 can be potentially used as an approach to avoid phagocytic clearance by macrophages in order to prolong the circulation time of drug delivery carriers and promoting delivery of drug to target sites
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