Down-regulation of macrophage I-A expression in tumor-bearing mice.
During the subcutaneous growth of a highly metastatic mammary adenocarcinoma line, C3-L4 in C3H/HeJ mice, there was a rapid decline in macrophage I-A expression in vivo. The incidence of I-A+ macrophage subset in the spleen declined from 90% to 10% or less within 5 days of tumor transplantation, with a parallel decline in their absolute number. I-A expression in these cells remained suppressed for a long time until tumors became necrotic and ulcerated. In spite of a low incidence (15-20%) of I-A+ macrophages in the normal peritoneal space, tumor transplantation caused a long-lasting decline in their incidence to one-fourth of the original level. Tumor-associated macrophages were predominantly I-A- throughout the tumor life span. Thus I-A- macrophages dominated in all anatomical compartments in tumor-bearing mice. Macrophage I-A expression was substantially restored (spleen) or stimulated (peritoneal space and tumor) in tumor-transplanted mice subjected to chronic indomethacin therapy in the drinking water, indicating a reversal of prostaglandin-mediated down-regulation of macrophage I-A expression in situ. Concomitantly, this therapy caused regression of the primary tumors and prevented lung metastasis. These results are relevant to the understanding of tumor-host interactions and its exploitation for immunotherapy.
Nelson
J A
JA
Department of Anatomy, University of Western Ontario, London, Canada.
Parhar
R S
RS
Scodras
J M
JM
Lala
P K
PK
D000818:Animals; D002452:Cell Count; D015232:Dinoprostone / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007213:Indomethacin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology
D000949:Histocompatibility Antigens Class II; D015232:Dinoprostone; D007213:Indomethacin