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.
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.
Gersuk
G M
GM
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Chang
W C
WC
Pattengale
P K
PK
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001667:Binding, Competitive; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology*; D007370:Interferon Type I / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000187:drug effects; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007166:Immunosuppressive Agents; D007370:Interferon Type I; D007376:Interleukin-2; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D017479:Receptors, Platelet-Derived Growth Factor