INTERLEUKIN-3 (IL-3) RECEPTORS ON RHESUS-MONKEY BONE-MARROW CELLS - SPECIES-SPECIFICITY OF HUMAN IL-3, BINDING CHARACTERISTICS, AND LACK OFCOMPETITION WITH GM-CSF

The relative affinity of recombinant human interleukin-3 (IL-3) bindin g to normal rhesus monkey bone marrow cells was found to be 25- to 50- fold less than that of homologous IL-3, which explained the species sp ecificity of human IL-3 observed when tested in Macaca species. In con trast, only a small difference was found between human and rhesus monk ey IL-3 in relative binding affinity for receptors on human acute myel ogenous leukemia (AML) cells, which confirmed that the species specifi city of IL-3 is largely unidirectional. The biological significance of the findings was demonstrated by direct in vivo comparison of the eff ects of high-dose recombinant rhesus monkey and human IL-3. The bindin g characteristics of IL-3 receptors on rhesus monkey bone marrow and p eripheral blood cells were further characterized by specific binding o f radiolabeled rhesus monkey IL-3. Scatchard analysis of two bone marr ow samples demonstrated high-affinity IL-3 receptors (25 and 80 sites/ cell, respectively; equilibrium dissociation constants [K-d] Of 8 and 3 pM/L) as well as low-affinity receptors (1070 and 1290 sites/cell; e quilibrium dissociation constants of 2600 and 1200 pM/L). In addition, IL-3 receptor expression was also detected on purified CD34-positive bone marrow cells. Competition by human granulocyte-macrophage colony- stimulating factor (GM-CSF) of IL-3 binding to high- or low-affinity r eceptors on rhesus monkey peripheral blood and bone marrow cells could not be demonstrated, which may indicate that the growth factor-specif ic alpha-subunits of the GM-CSF and IL-3 receptors are expressed predo minantly on different cell types.