Expression and regulation of IL-4 receptors on human monocytes and acute myeloblastic leukemic cells.
Evidence is presented that human monocytes and acute myeloblastic leukemic (AML) cells contain both high and low affinity binding sites for interleukin-4 (IL-4). On monocytes 183 +/- 132 high affinity binding sites per cell with a Kd of 60 +/- 29 pM and 1500 +/- 600 low affinity receptors with a Kd of 2.3 +/- 0.4 nM (X +/- S.D., n = 6) could be demonstrated. On AML cells (n = 11) a comparable number and binding affinity of IL-4 receptors were observed (77 +/- 36 high affinity receptors with Kd 72 +/- 31 pM and 2400 +/- 1000 low affinity receptors with Kd of 2.2 +/- 0.7 nM). In addition, no cross-competition was shown between radiolabeled IL-4 and IL-1-alpha, IL-3, IL-6, IL-7, G-CSF, and GM-CSF. Both types of receptors on monocytes as well as on leukemic blasts could be down-modulated in a similar fashion by IL-4 and activators of protein kinase C (PKC), but not by the calcium ionophore A23187. The down-modulation by PKC activators was caused by an increased internalization, degradation and release of radiolabeled IL-4 in the medium. Finally, the functionality of the IL-4 receptors were tested on AML cells with a 3H-thymidine proliferation assay. In 8/11 cases IL-4 affected AML proliferation. These data demonstrate two different binding sites for IL-4 on normal and leukemic cells, which can be modulated by external activation signals in an analogous way.
Department of Hematology, University of Groningen, The Netherlands.
A J
AJ
Wagteveld
A K
AK
van Zanten
M T
MT
Esselink
M R
MR
Halie
E
E
Vellenga
D002455:Cell Division / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate