[An adhesion dependent injury of target cell membrane by NK cell surface associated metaloprotease]

Natural killer (NK) cytotoxicity was assayed with P3-X63-Ag8-U1 (P3U-1) target cells which had been previously demonstrated to release endogenous alkaline phosphatase (AlP) on the attack of lymphocyte-activated killer cells). P3U-1 cells showed a definite sensitivity to the AlP-release test, but no response in the Cr-release test at all. The AlP-release was not inhibited by anti-perforin antibody, benzoate, phenyl-methyl-sulfonyl-fluoride, soybean trypsin inhibitor, Succinyl-Gly-Pro-Leu-Gly-Pro-amino-methyl-coumarin, or gamma-radiation to effector cells, but was inhibited by o-phenanthroline, anti-CD13 antibody, and anti-LFA-1 alpha antibody. The AlP-release from P3U-1, therefore, did not appear to be brought on by the NK cell-derived perforin, hydroxy-radical, granzymes or cytosolic proteases. The inhibition by o-phenanthroline and the antibody for CD13 (aminopeptidase N) or the adhesion factor in NK cells, however, indicated that the membrane of such cells with adhesion ligand to NK cells was probably susceptible to NK cell surface-associated metaloprotease in an adhesion dependent manner to the extent of some injury without complete perforation through the membrane.