Transferrin, iron, and serum lipids enhance or inhibit Mycobacterium avium replication in human macrophages.
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 micrograms/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 micrograms/mL. At 1000 micrograms/mL, apotransferrin no longer inhibited bacterial growth. Holotransferrin was not inhibitory, and at 500 micrograms/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.
Douvas
G S
GS
Webb-Waring Lung Institute, Division of Immunology, University of Colorado School of Dentistry, Denver 80262.
May
M H
MH
Crowle
A J
AJ
D000328:Adult; D005260:Female; D006679:HIV Seropositivity / Q000097:blood*; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009162:Mycobacterium avium / Q000187:drug effects* / Q000254:growth & development; D014168:Transferrin / Q000187:drug effects / Q000302:isolation & purification / Q000494:pharmacology*
D014168:Transferrin; D007501:Iron