INDUCTION OF NATURAL-KILLER-CELL MIGRATION BY MONOCYTE CHEMOTACTIC PROTEIN-1, PROTEIN-2 AND PROTEIN-3

Under certain physiological and pathological conditions, naturall killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced I-125-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active - though less potent attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.