Role of macrophages in the candidacidal activity of liposomal amphotericin B.
The role of macrophage activation in the candidacidal activity of liposome-incorporated (L) amphotericin B was investigated. Macrophages treated with L-amphotericin B killed Candida albicans more effectively than did macrophages treated with free (F) amphotericin B. However, macrophages treated with neither F- nor L-amphotericin B killed amphotericin B-resistant Candida tropicalis. In vivo stimulation of macrophages by intraperitoneal administration of thioglycollate, Freund's complete adjuvant, or heat-killed C. albicans followed by in vitro treatment with F- or L-amphotericin B, did not enhance their candidacidal activity. Intravenous administration of F- or L-amphotericin B did not augment the candidacidal activity of macrophages sensitized in vivo; however, sensitized macrophages showed enhanced killing compared with resident unstimulated cells. These studies suggest that macrophage-mediated enhancement of C. albicans killing may be due to uptake, transport, and delivery of L-amphotericin B to infected sites rather than to macrophage activation.
Mehta
R T
RT
Department of Bio-immunotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Poddar
S
S
Kalidas
M
M
Gomez-Flores
R
R
Dulski
K
K
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D002478:Cells, Cultured; D004337:Drug Carriers; D008081:Liposomes; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008855:Microscopy, Electron, Scanning
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B