1999 Volume 62 Issue 3 Pages 136-142
Natural killer (NK) cells have cytolytic activity without prior antigenic stimulation, and IL-2 activated NK cells are used for treatment of melanoma and renal cell carcinoma. However, the advantage of this immunotherapy is limited by the side effects of vascular damege and insufficient accumulation in the target tumor cells. Chemokines were initially reported as chemoattractant cytokines synthesized at inflammation sites. Monocyte chemoattractant protein-1 (MCP-1) is one of the CC-chemokine family and is reported to induce chemotaxis of monocytes, T cells and NK cells. We investigated the effect of MCP-1 on degranulation and cytotoxicity of the NK cell line, NK 3.3 cell. Expression of CD 16 and non-expression of CD 3 in the NK 3.3 cells were remarkably similar to the phenotype of fresh NK cells. In addition, cross-link stimulation of CD 2 and CD 16 induced degranulation from NK 3.3 cells. IL-2, but not MCP-1 or IL-12, markedly enhanced proliferation of NK 3.3 cells. MCP-1, IL-2 and IL-12 also induced degranulation from NK 3.3 cells. Kinetic studies revealed that MCP-1 mediated enhancement of degranulation occurred within one hour, and was sustained throughout the assay. MCP-1 also enhanced the cytotoxic activity of NK 3.3 cells in a dose-dependant manner. These results suggest that MCP-1 may enhance the cytotoxicity of NK cells as a result of granular exocytosis and produce an improvement in the immunotherapy.
