Macrophage effector mechanisms in melanoma in an experimental study.
BACKGROUND
The tumor-bearing state is known to induce immune dysfunction that contributes to increased infectious complications and tumor progression. However, the mechanisms underlying this immunosuppression remain unclear.


OBJECTIVE
Macrophage (MO) dysfunction may play a role in tumor-induced immunosuppression.


METHODS
Using a murine model, this study investigated the effects of melanoma growth on peritoneal macrophage effector molecule and prostaglandin production, MO-mediated cytotoxicity, and candidacidal mechanisms. Female C57BL/6 mice were inoculated with 106 B16 melanoma cells or a salt solution subcutaneously. Mice were euthanized 3 weeks later and peritoneal MOs were harvested and assayed for nitric oxide, superoxide anion, tumor necrosis factor alpha, and prostaglandin E(2)production. Macrophage-mediated cytotoxicity against B16 melanoma targets and MO candidacidal mechanisms were also measured.


RESULTS
Macrophage production of nitric oxide, superoxide anion, and tumor necrosis factor alpha were significantly decreased, while prostaglandin E(2)production was increased in MOs from melanoma-bearing mice. Concomitantly, MO-mediated cytotoxicity and candidacidal mechanisms were significantly impaired.


CONCLUSIONS
Melanoma growth leads to decreased MO effector molecule production, increased prostaglandin E(2)production, and impaired MO cytotoxic and candidacidal mechanisms. These results may help explain the observed increased infectious complications in the tumor-bearing host. Strategies aimed at restoring MO function may have therapeutic potential.
Naama
H A
HA
Department of Surgery, Weill Medical College of Cornell University, New York City, NY, USA.
Mack
V E
VE
Smyth
G P
GP
Stapleton
P P
PP
Daly
J M
JM
D000818:Animals; D002175:Candida / Q000276:immunology; D015232:Dinoprostone / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007165:Immunosuppression Therapy; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000276:immunology*; D008546:Melanoma, Experimental / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000032:analysis; D013481:Superoxides / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D015232:Dinoprostone