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 transduced with the lacZ gene. Liver and spleen macrophages were isolated and 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. An aggressive expansion of metastasis was correlated with a drop of NO production and ADA activity and with an increase of 5-N activity. To test the involvement of in situ activated Kupffer cells in an antimetastatic response, two immunotherapy protocols were used: i) active immunization with lymphoma cells and ii) adoptive transfer of antitumor immune spleen cells. Both treatments caused an upregulation of ADA activity and NO production in Kupffer cells, which correlated with host resistance against metastases.