These studies have investigated the mechanisms involved in the recruitment of murine NK cells to nonlymphoid organs in response to administration of biological response modifiers. A single dose of the BRM, poly ICLC, augmented hepatic NK activity and increased the number of liver-associated NK cells approximately 3-fold. As expected, treatment of mice with anti- asialo-GM1 eliminated both the hepatic influx of NK cells and the increase in poly ICLC induced liver NK activity. Moreover, similar results were obtained if poly ICLC-treated mice were injected with neutralizing rabbit antisera to TNF-alpha. Under these conditions, the number of hepatic NK cells was reduced 66% (reaching control levels). These results suggested that TNF-alpha may be a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells following BRM- treatment. Using the identical model system, concomitant administration of an alphaVCAM-1 monoclonal antibody and poly ICLC totally abrogated the increase in hepatic and pulmonary NK cell activity. Administration of an isotype matched antibody or an alphaICAM-1 antibody did not affect NK cell infiltration into these organs. These results would suggest that TNF-alpha is a principal cytokine mediating the recruitment of NK cells to organ parenchyma and that the endothelia adhesion molecule, VCAM-1, is intimately involved in this process. Future studies will be directed towards defining other recognition structures and cytokines relevant for the in vivo recruitment of NK cells into lungs and liver and the potential anti-tumor therapeutic consequences of this process.
