Transferrin, Iron, and Serum Lipids Enhance or Inhibit Mycobacterium avium Replication in Human Macrophages

• Published in: The Journal of infectious diseases 1993-04, Vol.167 (4), p.857-764
• Main Authors: Douvas, George S., May, Mary H., Crowle, Alfred J.
• Format: Article
• Language: English
• Subjects: Adult; AIDS; AIDS/HIV; Bacteriology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Growth, nutrition, cell differenciation; HIV Seropositivity - blood; Humans; Infections; Iron; Iron - pharmacology; Lipids; Macrophages; Macrophages - microbiology; Major Articles; Male; Microbiology; Middle Aged; Mycobacterium avium; Mycobacterium avium - drug effects; Mycobacterium avium - growth & development; Quaternary ammonium compounds; Sulfates; Transferrin - drug effects; Transferrin - isolation & purification; Transferrin - pharmacology; Transferrins; Triglycerides
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/167.4.857

Mycobacterium avium grows exponentially over 7 days in human macrophages when they are cultured in serumless medium. Normal serum inhibits this replication. When serum lipids were extracted using chloroform, the inhibitor was present in the lipid-free component. The lipid extract significantly enhanced M. avium replication. Iron (Fe2+)added at 8-80 µg/mL to infected macrophage cultures in serum resulted in enhanced mycobacterial replication. Serum-induced inhibition of bacterial growth in serumless medium could be duplicated with apotransferrin at 50-500 µg/mL. At 1000 µg/mL, apotransferrin no longer inhibited bacterial growth. Holotransferrin was not inhibitory, and at 500 µg/mL, it enhanced M. avium growth. Depletion of the transferrin in serum by affinity chromatography using goat anti-transferrin on protein G-Sepharose removed inhibitory activity. These results indicate that transferrin levels, transferrin saturation, iron levels, and serum lipids can profoundly alter the replication of M. avium in association with macrophages.