Inhibition of ADAM17 reduces antibody cross-linking induced shedding of CD16 and CD62L, and increases IFN-γ production by CD16 signaling. Purified NK cells (n = 8) were cross-linked with plate bound anti-immunoglobulin, -CD16, -2B4, and -NKp46, and with K562 cells in the presence of 10 μM ADAM 17 inhibitor (white bars) or no inhibitor (black bars). After 5 hours incubation surface expression of CD16 (A), CD62L (B) intracellular IFN-γ (C, left panel) and intracellular TNF-α (D) was measured. Bars represent mean ± SEM. NK cells incubated without ADAM17 inhibitor were compared with NK cells incubated with ADAM17 inhibitor using the paired t test. Statistical significance is indicated as: *P ≤ .05; **P < .01; ***P < .001.