Inhibition of human natural killer cell activity by platelet-derived growth factor (PDGF). III. Membrane binding studies and differential biological effect of recombinant PDGF isoforms.
We have previously reported that platelet-derived growth factor (PDGF) substantially inhibits human natural killer (NK) cell cytotoxicity, and that NK cells possess high-affinity surface binding sites for the PDGF-AB isoform. In this communication, we present direct evidence for the presence of A-type (alpha) PDGF receptors on human NK cells by demonstrating that human NK cells have approximately 150,000 high-affinity, surface binding sites for recombinant (r)PDGF-AA and approximately 300,000 high-affinity, surface binding sites for rPDGF-BB. This was determined by the competitive binding of 125I-labelled rPDGF-AA or 125I-labelled rPDGF-BB and homologous unlabelled rPDGF-AA or rPDGF-BB to FACS-sorted, CD16+ lymphoid (NK) cells, and Scatchard analysis of these data. In addition, we also demonstrate that the various isoforms of PDGF have differential effects on NK-cell cytotoxicity. Physiological quantities (100 ng/ml) of rPDGF-BB homodimers, highly purified PDGF-AB heterodimers from outdated platelets, and rPDGF-AB heterodimers substantially inhibited NK-cell cytotoxicity in both a dose- and time-dependent manner. In contrast, pretreatment of NK cells with equivalent nanogram amounts of rPDGF-AA homodimers resulted in a significantly weaker inhibitory effect on NK-cell cytotoxicity as compared with the PDGF-BB and PDGF-AB isoforms. The implications of these findings are discussed.
Gersuk
G M
GM
Department of Pathology, Children's Hospital of Los Angeles, California 90027.
Westermark
B
B
Mohabeer
A J
AJ
Challita
P M
PM
Pattamakom
S
S
Pattengale
P K
PK
D000328:Adult; D000943:Antigens, Differentiation / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology
D000943:Antigens, Differentiation; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D017479:Receptors, Platelet-Derived Growth Factor