Internalization of human interleukin 4 and transient down-regulation of its receptor in the CD23-inducible Jijoye cells.
Human interleukin 4 (IL-4) specifically induces the low affinity receptor for IgE (Fc epsilon R2/CD23) on the surface of the Burkitt lymphoma cell line Jijoye. At 4 degrees C 125I-IL-4 specifically binds to high affinity receptors (Kd = 4-10 x 10(-11) M; Bmax, 600-1,200 sites/cell). Following a rapid temperature shift from 4 to 37 degrees C, 80% of the receptor-bound 125I-IL-4 disappeared from the cell surface within 20 min (t1/2 = 8.9 min). For every two internalized molecules of IL-4 (t1/2 = 13 min), one molecule of IL-4 dissociated from the cell surface (t1/2 = 25 min). More than 90% of the internalized IL-4 was released in a degraded form into the medium following first order kinetics (t1/2 = 68 min). Internalization was inhibited by cytoskeletal disrupting and lysosomotropic agents. Incubating cells with 1 nM IL-4 resulted in a rapid down-regulation of IL-4 receptors (75% loss after 2 h); a reexpression of receptor to control level occurred after 20 h in spite of the presence of a large excess of IL-4. Reexpression was delayed by chloroquine and blocked by cycloheximide and actinomycin D. By using the cross-linking agent bis(sulfosuccinimidyl)suberate, three polypeptides of Mr 130,000, 80,000, and 70,000 were specifically labeled with 125I-IL-4. These three polypeptides coordinately disappeared and reappeared with the 125I-IL-4 binding sites. The induction of Fc epsilon R2/CD23 required prolonged incubation (greater than 8 h) with IL-4 and thus may be dependent on the reexpression of IL-4 receptor.
Galizzi
J P
JP
UNICET, Laboratory for Immunological Research, Dardilly, France.
Zuber
C E
CE
Cabrillat
H
H
Djossou
O
O
Banchereau
J
J
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001386:Azides / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004705:Endocytosis; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4; D007378:Interleukins / Q000378:metabolism*; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D014158:Transcription, Genetic
D000944:Antigens, Differentiation, B-Lymphocyte; D001386:Azides; D007378:Interleukins; D011961:Receptors, Fc; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D003571:Cytochalasin B; D002738:Chloroquine