4.5 Article

Stimulation of phagocytic activity of alveolar macrophages toward artificial microspheres by infection with mycobacteria

Journal

PHARMACEUTICAL RESEARCH
Volume 25, Issue 6, Pages 1420-1430

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-007-9525-8

Keywords

alveolar macrophage; phagocytosis; polymer microspheres; pulmonary delivery; tuberculosis

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Purpose. The purpose of this study is to know the effect of uptake of mycobacteria on the phagocytic activity of alveolar macrophage (M phi) 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-alpha (TNF-alpha) and nitric oxide (NO) were examined using alveolar M phi cell NR8383 after they had phagocytosed Mycobacterium bovis Caimette-Guerin (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 M phi cells within 2 days. The phagocytosis caused generation of TNF-alpha 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-alpha or NO, but that of E. coh 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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