No interactions between heparin and atacicept, an antagonist of B cell survival cytokines.

Détails

ID Serval
serval:BIB_72714CC62B0C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
No interactions between heparin and atacicept, an antagonist of B cell survival cytokines.
Périodique
British journal of pharmacology
Auteur(s)
Kowalczyk-Quintas C., Willen D., Willen L., Golob M., Schuepbach-Mallepell S., Peter B., Eslami M., Vigolo M., Broly H., Samy E., Yalkinoglu Ö., Schneider P.
ISSN
1476-5381 (Electronic)
ISSN-L
0007-1188
Statut éditorial
In Press
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Résumé
The TNF family ligands, B cell activating factor of the TNF family (BAFF, also known as B lymphocyte stimulator, BLyS) and a proliferation-inducing ligand (APRIL), share the transmembrane activator and calcium-modulator and cyclophilin ligand (CAML)-interactor (TACI) as one of their common receptors. Atacicept, a chimeric recombinant TACI/IgG1-Fc fusion protein, inhibits both ligands. TACI and APRIL also bind to proteoglycans (PGs) and to heparin that is structurally related to PGs. It is unknown whether the portion of TACI contained in atacicept can bind directly to PGs, or indirectly via APRIL, and whether this could interfere with the anti-coagulant properties of heparin.
Binding of atacicept and APRIL to PG-positive cells was measured by FACS. Activities of heparin and atacicept were measured with activated factor Xa inhibition and cell-based assays. The impact of heparin on circulating atacicept was monitored in mice.
Atacicept did not bind to PG-positive cells, but when complexed to APRIL could do so indirectly via APRIL. Multimers of atacicept obtained after exposure to cysteine or BAFF 60mer bound directly to PGs. Atacicept alone, or in complex with APRIL, or in a multimeric form did not interfere with heparin activity in vitro. Conversely, heparin did not influence inhibition of BAFF and APRIL by atacicept and did not change circulating levels of atacicept.
Lack of detectable interference of APRIL-bound or free atacicept on heparin activity makes it unlikely that atacicept at therapeutic doses will interfere with the function of heparin in vivo.
Mots-clé
APRIL, BAFF, BLyS, TACI, atacicept, heparan sulfate proteoglycans, heparin
Pubmed
Création de la notice
06/08/2019 16:25
Dernière modification de la notice
21/08/2019 5:35
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