Aureobasidium pullulans culture supernatant significantly stimulates R-848-activated phagocytosis of PMA-induced THP-1 macrophages. (August 2013)

• Record Type: Journal Article
• Authors: Tamegai, Hidekazu; Takada, Yuka; Okabe, Mitsuyasu; Asada, Yukoh; Kusano, Kisato; Katagiri, Yohko U.; Nagahara, Yukitoshi
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 35:Number 4(2013:Aug.)
• Page Start: 455
• Page End: 461
• Publication Date: 2013-08
• Subjects: Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2013.800106
• Languages: English
• ISSNs: 0892-3973

Abstract

<abstract> <title>Abstract</title> <p>Toll-like receptors (TLRs), which recognize a wide range of microbial pathogens and pathogen-related products, play important roles in innate immunology. Macrophages have a variety of TLRs, and pathogen binding to TLR resulted in the activation of macrophages. R-848, an immune response modifier, is an analog of imidazoquinoline derivative and binds to an endosome-localized TLR to exert an anti-viral response on leukocytes. In the present study, we verified that co-treatment of R-848 with other TLR agonists would enhance immune response. The culture supernatant of <italic>Aureobasidium pullulans</italic> (<italic>A. pullulans</italic>, which contains predominantly soluble β-glucan), which binds to cell membrane-localized TLR, and to C-type lectin receptor Dectin-1, was treated together with R-848 to THP-1 macrophages. Compared to R-848 treatment alone, co-treatment of R-848 with <italic>A. pullulans</italic> culture supernatant significantly augmented TNF-α and IL-12p40 cytokine expression. Next, we investigated whether or not apoptotic cell uptake would be increased by co-treatment of R-848 with <italic>A. pullulans</italic> culture supernatant. To detect engulfed apoptotic cells, we induced apoptosis in human lymphoma Jurkat cells by 5-fluorouracil and stained them with fluorescent dye 5(6)-carboxytetramethylrhodamine (TAMRA), whereas THP-1 macrophage was labeled with fluorescein isothiocyanate-anti-CD14 and determined the percentage increase in TAMRA-positive THP-1 macrophages by flow cytometric assay. Since R-848 or <italic>A. pullulans</italic> treatment alone stimulated THP-1 macrophages to induce phagocytosis, co-treatment of R-848 with <italic>A. pullulans</italic> culture supernatant significantly augmented phagocytosis of apoptotic Jurkat cells. These results suggest that the activation of several different innate immune receptor pathways may enhance the immune response of R-848 significantly.</p> </abstract>