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Stimulation of Phagocytic Activity of Alveolar Macrophages Toward Artificial Microspheres by Infection with Mycobacteria

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Abstract

Purpose

The purpose of this study is to know the effect of uptake of mycobacteria on the phagocytic activity of alveolar macrophage (Mφ) cells toward poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP-PLGA MS).

Materials and Methods

Biological functions such as phagocytic activity toward PLGA MS loaded with fluorescent coumarin (cPLGA MS) and toward polystyrene latex MS (PSL MS), and generation of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were examined using alveolar Mφ cell NR8383 after they had phagocytosed Mycobacterium bovis Calmette-Guérin (BCG), heat-killed BCG (h-kBCG) or Escherichia coli.

Results

The ingestion of BCG, h-kBCG, and E. coli did not affect the viability of the Mφ cells within 2 days. The phagocytosis caused generation of TNF-α and NO, being more significant with E. coli than with both types of BCGs. The phagocytosis of both types of BCGs stimulated the phagocytic uptake of cPLGA and PSL MS’s, which took place prior to the generation of TNF-α or NO, but that of E. coli suppressed the uptake of both MS’s.

Conclusion

Mycobacterial infection stimulated the phagocytic uptake toward cPLGA MS. These results suggest that RFP-PLGA MS is favorable for overcoming tuberculosis.

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Abbreviations

BCG:

Mycobacterium bovis Calmette-Guérin

h-kBCG:

heat-killed BCG

CFU:

colony-forming units

ELISA:

enzyme-linked immunosorbent assay

FBS:

fetal bovine serum

Mφ:

macrophage

MOI:

multiplicity of infection

MTB:

Mycobacterium tuberculosis

MS:

microspheres

NO:

nitric oxide

PBS:

phosphate-buffered saline

PLGA:

poly(lactic-co-glycolic) acid

cPLGA MS:

PLGA MS loaded with coumarin 6

RFP-PLGA MS:

PLGA MS loaded with rifampicin

PSL MS:

polystyrene latex MS

RFP:

rifampicin

TNF-α:

tumor necrosis factor-α

WST-8:

2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt

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Acknowledgements

This study was supported, in part, by the “High-Tech Research Center” Project for Private Universities with a matching fund subsidy from MEXT (Ministry for Education, Culture, Sports, Science, and Technology) of Japan, 2004–2008, and by a grant-in-aid for scientific research from MEXT (No. 15300170 to H.T.).

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan

    Keiji Hirota, Keishiro Tomoda, Kimiko Makino & Hiroshi Terada

  2. Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan

    Keiji Hirota, Keishiro Tomoda, Hiroyuki Inagawa, Chie Kohchi, Gen-Ichiro Soma, Kimiko Makino & Hiroshi Terada

  3. Institute for Health Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima, 770-8514, Japan

    Chie Kohchi & Gen-Ichiro Soma

  4. Department of Applied Aquabiology, National Fisheries University, 2-7-1 Nagata-Honmachi, Shimonoseki, Yamaguchi, 759-6595, Japan

    Hiroyuki Inagawa

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  1. Keiji Hirota
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  2. Keishiro Tomoda
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Correspondence to Hiroshi Terada.

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Hirota, K., Tomoda, K., Inagawa, H. et al. Stimulation of Phagocytic Activity of Alveolar Macrophages Toward Artificial Microspheres by Infection with Mycobacteria. Pharm Res 25, 1420–1430 (2008). https://doi.org/10.1007/s11095-007-9525-8

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  • DOI: https://doi.org/10.1007/s11095-007-9525-8

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