IN-SITU ACTIVATED MACROPHAGES ARE INVOLVED IN HOST-RESISTANCE TO LYMPHOMA METASTASIS BY PRODUCTION OF NITRIC-OXIDE

We studied nitric oxide (NO) production, adenosine deaminase (ADA) and 5'-nucleotidase (5-N) activity as a function of macrophage activation in the model of spontaneous metastasis of ESbL T lymphoma cells trans duced with the lacZ gene. Liver and spleen macrophages were isolated a nd examined directly ex vivo without further experimental manipulation . Transient arrest of liver metastasis was accompanied by an increase of NO production and ADA activity and by a decrease of 5-N activity. A n aggressive expansion of metastasis was correlated with a drop of NO production and ADA activity and with an increase of 5-N activity. To t est the involvement of in situ activated Kupffer cells in an antimetas tatic response, two immunotherapy protocols were used: i) active immun ization with lymphoma cells and ii) adoptive transfer of antitumor imm une spleen cells. Both treatments caused an upregulation of ADA activi ty and NO production in Kupffer cells, which correlated with host resi stance against metastases.