Inhibition of human natural killer cell activity by platelet-derived growth factor. II. Membrane binding studies, effects of recombinant IFN-alpha and IL-2, and lack of effect on T cell and antibody-dependent cellular cytotoxicity.

Abstract

We have previously reported that a 2-h pre-treatment with physiologic (nanogram) quantities of the naturally occurring biologic substance, platelet-derived growth factor (PDGF), significantly inhibits human NK cell activity (cytotoxicity) in a dose-dependent manner as measured against the NK-sensitive target K-562, as well as the single-cell binding of human NK cells to K-562 targets (i.e., conjugate formation). In this study, we have completed a more detailed and longer time course evaluation of PDGF-mediated human NK cell inhibition, and demonstrate a more marked inhibition of human NK cells at 8 to 20 h as compared to 2 h. We also show that either rIFN-alpha or IL-2 reverses the PDGF-mediated NK cell inhibition; and furthermore, that PDGF does not inhibit the lymphokine augmented NK activity of recombinant alpha-IFN or IL-2-activated human NK cells. In addition, we have further demonstrated that PDGF does not inhibit cytotoxic T cell activity as generated in the MLR, nor does PDGF significantly inhibit antibody-dependent cellular cytotoxicity. Finally, we have demonstrated that human NK cells have roughly 12,000 high-affinity, surface binding sites for PDGF, as determined by the competitive binding of 125I-labeled purified PDGF and unlabeled PDGF to B73.1+ FACS-sorted lymphoid (NK) cells, and Scatchard analysis of these data. The implications of these findings are discussed.