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

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Ressource 1Download: 200. Kowalczyk et al with Suppl.pdf (6253.50 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_72714CC62B0C
Type
Article: article from journal or magazin.
Collection
Publications
Title
No interactions between heparin and atacicept, an antagonist of B cell survival cytokines.
Journal
British journal of pharmacology
Author(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
Publication state
Published
Issued date
10/2019
Peer-reviewed
Oui
Volume
176
Number
20
Pages
4019-4033
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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 and to heparin that is structurally related to proteoglycans. It is unknown whether the portion of TACI contained in atacicept can bind directly to proteoglycans, or indirectly via APRIL, and whether this could interfere with the anti-coagulant properties of heparin.
Binding of atacicept and APRIL to proteoglycan-positive cells was measured by FACS. Activities of heparin and atacicept were measured with activated factor Xa inhibition and cell-based assays. Effects of heparin on circulating atacicept was monitored in mice.
Atacicept did not bind to proteoglycan-positive cells, but when complexed to APRIL could do so indirectly via APRIL. Multimers of atacicept obtained after exposure to cysteine or BAFF 60-mer bound directly to proteoglycans. 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.
Keywords
APRIL, BAFF, BLyS, TACI, atacicept, heparan sulfate proteoglycans, heparin
Pubmed
Web of science
Open Access
Yes
Create date
06/08/2019 17:25
Last modification date
17/01/2020 8:09
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