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Inhibition of Human Natural Killer Cell Activity by Platelet‐Derived Growth Factor (PDGF)
Author(s) -
GERSUK G. M.,
WESTERMARK B.,
MOHABEER A. J.,
CHALLITA P. M.,
PATTAMAKOM S.,
PATTENGALE P. K.
Publication year - 1991
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1991.tb02522.x
Subject(s) - cytotoxicity , platelet derived growth factor receptor , microbiology and biotechnology , growth factor , receptor , biology , platelet derived growth factor , cell , natural killer cell , cell culture , in vitro , gene isoform , chemistry , biochemistry , gene , genetics
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 125 I‐labelled rPDGF‐AA or 125 I‐labelled rPDGF‐BB and homologous unlabelled rPDGF‐AA or rPDGF‐BB to FACS‐sorted, CDl6 + lymphoid (NK)cells, and Scatchard analysis of these data. In addition, we also demonstrated 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cytotoxicity, Physiological quantities (100 ng/ml) of rPDGF‐BB homodimers, highly purified PDGF‐AB heterodimers from outdated platelets, and rPDGF‐AB heterodimers substantially inhibited NK‐cell cytotoxicity in both a dose‐ and time‐dependent manner.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 und PDGF‐AB isoforms. The implications of these findings are discussed.