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


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 Mphi 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 Mphi 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. coli suppressed the uptake of both MS's.


CONCLUSIONS
Mycobacterial infection stimulated the phagocytic uptake toward cPLGA MS. These results suggest that RFP-PLGA MS is favorable for overcoming tuberculosis.
Hirota
Keiji
K
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Tomoda
Keishiro
K
Inagawa
Hiroyuki
H
Kohchi
Chie
C
Soma
Gen-Ichiro
G
Makino
Kimiko
K
Terada
Hiroshi
H
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage; D016676:Macrophages, Alveolar / Q000276:immunology*; D008863:Microspheres; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D012293:Rifampin / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid; D012293:Rifampin