Hypertriglyceridemic serum, very low density lipoprotein, and iron enhance Mycobacterium avium replication in human macrophages.
The growth of Mycobacterium avium 7497, serovar 4, in cultured human macrophages is enhanced by Fe3+ and serum lipids over 7 days. Iron (1-80 micrograms/mL) added to macrophages cultured in normal serum resulted in 10-fold increases in growth. If iron-supplemented macrophages were cultured in serum from hypertriglyceridemic donors after infection, M. avium growth increased 10(3)- to 10(4)-fold. Without macrophages, differences in bacterial growth between sera were not seen. Removal of very low density lipoprotein (VLDL) eliminated the differences between sera. Isolated VLDL from hyperlipidemic serum resulted in 10(5)-fold increases in growth over that seen with VLDL from normal sera. Accelerated M. avium growth in macrophages cultured with hyperlipidemic serum was partly inhibited by the addition of superoxide dismutase (1000 IU/mL). Results suggest that iron stimulates O2-induced oxidation of VLDL and its subsequent accumulation in macrophages. The resultant iron- and lipid-laden cells become excellent hosts for mycobacterial growth.
Department of Basic Sciences and Oral Research, School of Dentistry, University of Colorado Health, Sciences Center, Denver 80262.
G S
GS
Douvas
M H
MH
May
J R
JR
Pearson
E
E
Lam
L
L
Miller
N
N
Tsuchida
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D000328:Adult; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007501:Iron / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009162:Mycobacterium avium / Q000254:growth & development*; D013482:Superoxide Dismutase / Q000494:pharmacology
D008079:Lipoproteins, VLDL; D007501:Iron; D013482:Superoxide Dismutase