Reference : Neutralizing monoclonal antibodies can potentiate IL-5 signaling
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Neutralizing monoclonal antibodies can potentiate IL-5 signaling
Zabeau, L. [> >]
Van der Heyden, J. [> >]
Broekaert, D. [> >]
Verhee, A. [> >]
Vandekerckhove, J. [> >]
Wu, S. J. [> >]
Chaiken, I. [> >]
Heinrich, P. [> >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Tavernier, J. [> >]
European Journal of Immunology
VCH Verlagsgesellschaft
Yes (verified by ORBilu)
[en] Tumor Cells, Cultured ; Interleukin-5 ; Immunoglobulin Fab Fragments ; Hybrid Cells ; Humans ; Epitopes ; Epitope Mapping ; Drug Synergism ; Dose-Response Relationship, Immunologic ; Cell Line ; Cell Division ; Antibodies, Monoclonal ; Janus Kinase 2 ; Mice ; Models, Biological ; Transfection ; Signal Transduction ; Receptors, Interleukin-5 ; Receptors, Interleukin ; Receptor Aggregation ; Rats ; Proto-Oncogene Proteins ; Protein-Tyrosine Kinases ; Protein Conformation ; Neutralization Tests ; Models, Molecular ; Animals
[en] IL-5 is a major determinant in the survival, differentiation and effector-functions of eosinophils. It mediates its effect upon binding and activation of a membrane bound receptor (R), composed of a ligand-specific alpha-chain and a beta-chain, shared with the receptors for IL-3 and granulocyte-macrophage colony-stimulating factor. We have generated and mapped the epitopes of three monoclonal antibodies (mAb) directed against this cytokine: the strong neutralizing mAb 5A5 and 1E1, and the very weak neutralizing mAb H30. We found that H30 as well as 5A5 can increase proliferation above the level induced by human (h)IL-5 alone, in a JAK-2-dependent manner, and at every sub-optimal hIL-5 concentration analyzed. This effect is dependent on mAb-mediated cross-linking of IL-5R complexes, and is only observed on cell lines expressing a hybrid human/mouse IL-5Ralpha-chain. We discuss these findings in view of the stoichiometric and topological requirements for an activated IL-5R. Since humanized anti-IL-5 mAb are currently in clinical testing, our findings imply that such mAb should be carefully evaluated for their potentiating effects.

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