Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels.
To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL-3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c-kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL-3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL-3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.
van Gils
F C
FC
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
van Teeffelen
M E
ME
Neelis
K J
KJ
Hendrikx
J
J
Burger
H
H
van Leen
R W
RW
Knol
E
E
Wagemaker
G
G
Wognum
A W
AW
D000818:Animals; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006636:Histamine Release; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D008253:Macaca mulatta / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000032:analysis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D019947:Receptors, Interleukin-6
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D019947:Receptors, Interleukin-6; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases