TRANSFORMING GROWTH-FACTOR-BETA-1 IS CHEMOTACTIC FOR INTERLEUKIN-2-ACTIVATED NATURAL-KILLER-CELLS

We examined the effect of transforming growth factor-beta1 (TGF-beta1) on the in vitro motility of interleukin-2-activated natural killer (I ANK) cells. Low doses of TGF-beta1 (0.01 or 0.1 ng/ml) are chemotactic for these cells as determined by modified Boyden chamber assay. IANK cells bind biotinylated TGF-beta suggesting that they express receptor s for this cytokine. TGF-beta1-induced IANK cell chemotaxis was inhibi ted by protein kinase C inhibitors, such as staurosporine and H7. The role of calcium mobilization in TGF-beta1 activity was also examined; the inhibitor of intracellular Ca2+, TMB-8, inhibited TGF-beta1-induce d IANK cell chemotaxis. Supporting the role for Ca2+ mobilization is t he ability of low doses of TGF-beta1 to induce the recruitment of intr acellular Ca2+ as determined by a fura-2-AM-loaded-cell assay.