Functional analysis of the interleukin-5 receptor antagonist peptide, AF18748.
AF18748 is a dimeric peptide of 2 x 19 amino acids that specifically binds to the alpha-chain of the human IL-5 receptor (IL-5R), preventing binding of IL-5 and acting as a receptor antagonist. However, the peptide acts by inducing alpha-chain dimerization, and we therefore set out to investigate whether this peptide would have any residual agonist activity. AF18748 was unable to induce activation of a number of signal transduction pathways, but was able to specifically block IL-5-dependent signal transduction. The peptide was unable to support the survival and proliferation of the cytokine dependent cell line, Ba/F3-IL-5R, and was unable to prime the respiratory burst, or induce adhesion, migration or survival of primary human eosinophils. In each case the AF18748 functioned as an antagonist. These data suggest that AF18748 may be useful to specifically modulate eosinophil function in vivo.
Rosas
Marcela
M
Department of Pulmonary Diseases, G03.550, University Medical Centre, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Uings
Iain J
IJ
van Aalst
Cornelli
C
Lammers
Jan-Willem J
JW
Koenderman
Leo
L
Coffer
Paul J
PJ
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053649:Receptors, Interleukin-5; D015398:Signal Transduction / Q000187:drug effects
C505964:AF 18748; D015848:Interleukin-5; D010455:Peptides; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5