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Neutralizing monoclonal antibodies can potentiate IL‐5 signaling
Journal article   Open access   Peer reviewed

Neutralizing monoclonal antibodies can potentiate IL‐5 signaling

Lennart Zabeau, José Van der Heyden, Daniël Broekaert, Annick Verhee, Joël Vandekerckhove, Sheng‐Jiun Wu, Irwin Chaiken, Peter Heinrich, Iris Behrmann and Jan Tavernier
European journal of immunology, v 31(4), pp 1087-1097
Apr 2001
DOI: https://doi.org/10.1002/1521-4141(200104)31:4<1087::AID-IMMU1087>3.0.CO;2-Q
PMID: 11298333
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1002/1521-4141(200104)31:4<1087::aid-immu1087>3.0.co;2-qView
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open
url
https://doi.org/10.1002/1521-4141(200104)31:4<1087::AID-IMMU1087>3.0.CO;2-QView
Published, Version of Record (VoR) Open

Abstract

IL‐5 receptor Cellular proliferation Antibody IL‐5
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 α‐chain and a β‐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‐5Rα‐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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17 citations in Web of Science
38 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
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