Interleukin-3 (IL-3) receptors on rhesus monkey bone marrow cells: species specificity of human IL-3, binding characteristics, and lack of competition with GM-CSF.
The relative affinity of recombinant human interleukin-3 (IL-3) binding 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 specificity of human IL-3 observed when tested in Macaca species. In contrast, only a small difference was found between human and rhesus monkey IL-3 in relative binding affinity for receptors on human acute myelogenous leukemia (AML) cells, which confirmed that the species specificity of IL-3 is largely unidirectional. The biological significance of the findings was demonstrated by direct in vivo comparison of the effects of high-dose recombinant rhesus monkey and human IL-3. The binding characteristics of IL-3 receptors on rhesus monkey bone marrow and peripheral blood cells were further characterized by specific binding of radiolabeled rhesus monkey IL-3. Scatchard analysis of two bone marrow samples demonstrated high-affinity IL-3 receptors (25 and 80 sites/cell, respectively; equilibrium dissociation constants [Kd] of 8 and 3 pM/L) as well as low-affinity receptors (1070 and 1290 sites/cell; equilibrium 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 receptors on rhesus monkey peripheral blood and bone marrow cells could not be demonstrated, which may indicate that the growth factor-specific alpha-subunits of the GM-CSF and IL-3 receptors are expressed predominantly on different cell types.
van Gils
F C
FC
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
Budel
L M
LM
Burger
H
H
van Leen
R W
RW
Löwenberg
B
B
Wagemaker
G
G
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001667:Binding, Competitive; D001853:Bone Marrow / Q000737:chemistry* / Q000648:ultrastructure; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D016185:Receptors, Interleukin-3 / Q000032:analysis* / Q000378:metabolism*; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018952:Antigens, CD34; D007377:Interleukin-3; D007457:Iodine Radioisotopes; D016185:Receptors, Interleukin-3; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor