EXPRESSION OF TYPE-I INSULIN-LIKE GROWTH-FACTOR RECEPTORS ON HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Insulin-like growth factor-I and -II (IGF-I and IGF-II), both of which bind to type I IGF receptors, can modulate certain functions of the immune system. We, therefore, studied the expression of type I IGF receptors on purified subpopulations of peripheral blood mononuclear cells. Using two-color flow cytometry, specific binding of a monoclonal antibody directed against the type I IGF receptor (alphaIR3) was found in every subpopulation. Relatively high numbers of receptors were detected on monocytes, natural killer cells, and CD4+ T-helper cells, an intermediate number of receptors on CD8+ suppressor/cytotoxic T-cells, and a relatively low number of receptors on B-cells. The presence of these receptors was confirmed by specific binding of [I-125] IGF-I to purified subpopulations. AlphaIR3 inhibited the binding of [I-125] IGF-I. The specific binding of [I-125]IGF-I to monocytes could be completely inhibited by IGF-II and insulin, but higher doses of these peptides were needed than of IGF-I. Scatchard analysis revealed the presence of 734 +/- 426 receptors/monocyte, with a K(d) of 0.23 +/- 0.05 nm. A lower number of receptors (230 +/- 52), but with a higher affinity (K(d) = 0.05 +/- 0.02 nm), was found on purified T-cells. The positive effect of IGF-I on natural killer cell cytotoxicity indicates that the type I IGF receptors on this cell type are functional. The possibility that IGF-I mediates hormonal effects on the immune system is discussed.