Factor VIII Fc Fusion Protein but not FVIII Drives Human Monocyte-Derived Dendritic Cell Activation via FcγRIIa.
Journal
HemaSphere
ISSN: 2572-9241
Titre abrégé: Hemasphere
Pays: United States
ID NLM: 101740619
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
19
07
2019
accepted:
26
11
2019
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
20
2
2020
Statut:
epublish
Résumé
This study compares the effect of recombinant Factor VIII Fc fusion protein (rFVIII-Fc) with recombinant FVIII (rFVIII) on monocyte-derived dendritic cells (moDC's). Cells treated with rFVIII-Fc showed morphological changes typical for cell activation, had a significant up-regulation of cell activation markers and produced higher levels of pro-inflammatory cytokines. Even after stimulation with Lipopolysaccharides, the addition of rFVIII-Fc led to increased expression of activation markers, indicating that rFVIII-Fc is capable of amplifying the maturation signal. On the contrary, cultivation of moDC's with rFVIII did not alter cell morphology or increase surface activation marker expression and pro-inflammatory cytokine production. The binding of the Fc domain to the activating Fcγ receptor IIa (FcγRIIa) can cause cell activation. Therefore, the effect of rFVIII-Fc on FcγRIIa was analyzed in detail. Cultivation of moDC's with rFVIII-Fc led to increased phosphorylation of FcγRIIa, which was not detected for rFVIII. Blocking FcγRIIa prior to the cultivation with rFVIII-Fc significantly reduced the activating effect of rFVIII-Fc, indicating that rFVIII-Fc-induced moDC activation was caused by FcγRIIa. Moreover, rFVIII-Fc bound to
Identifiants
pubmed: 32072146
doi: 10.1097/HS9.0000000000000330
pii: HemaSphere-2019-0144
pmc: PMC7000470
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e330Informations de copyright
Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.
Déclaration de conflit d'intérêts
The authors have indicated they have no potential conflicts of interest to disclose.
Références
Front Immunol. 2015 Nov 23;6:584
pubmed: 26635798
Eur J Immunol. 2002 Mar;32(3):634-43
pubmed: 11857337
Parasite Immunol. 2009 Sep;31(9):529-38
pubmed: 19691552
Immunol Rev. 2009 May;229(1):114-25
pubmed: 19426218
J Exp Med. 2000 Oct 2;192(7):1027-34
pubmed: 11015443
Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19571-8
pubmed: 19036920
Annu Rev Immunol. 2000;18:767-811
pubmed: 10837075
Haemophilia. 2015 Jan;21 Suppl 1:1-12
pubmed: 25472812
MAbs. 2010 May-Jun;2(3):256-65
pubmed: 20400861
Adv Immunol. 2007;96:179-204
pubmed: 17981207
Vaccine. 2011 Apr 5;29(16):2968-77
pubmed: 21329775
Cell Immunol. 2016 Mar;301:82-9
pubmed: 26547364
J Immunol. 2016 Jan 15;196(2):624-36
pubmed: 26663720
Blood Rev. 2017 Sep;31(5):339-347
pubmed: 28716211
Nat Rev Immunol. 2008 Jan;8(1):34-47
pubmed: 18064051
Int Immunol. 2002 Sep;14(9):1027-37
pubmed: 12202400
Biochemistry. 1998 Sep 1;37(35):12172-7
pubmed: 9724530
Nat Rev Immunol. 2004 May;4(5):336-47
pubmed: 15122199
Cell Immunol. 2016 Mar;301:30-9
pubmed: 26775174
J Leukoc Biol. 2001 Nov;70(5):715-22
pubmed: 11698490
Eur J Immunol. 2004 Jan;34(1):156-64
pubmed: 14971041
Cell Immunol. 2016 Mar;301:40-8
pubmed: 26723503
Recept Channels. 1998;5(5):243-53
pubmed: 9666518
Blood. 2018 May 17;131(20):2205-2214
pubmed: 29588277
Curr Biol. 2004 Nov 23;14(22):R965-7
pubmed: 15556856
Blood. 2012 Mar 29;119(13):3031-7
pubmed: 22223821
Immunity. 2017 Dec 19;47(6):1051-1066.e12
pubmed: 29262348
Int J Biol Macromol. 2018 Nov;119:496-504
pubmed: 30063930
Mol Immunol. 2010 Jul;47(11-12):2074-82
pubmed: 20444501
Blood. 2012 Mar 29;119(13):3024-30
pubmed: 22246033
Bioengineering (Basel). 2017 May 17;4(2):
pubmed: 28952523
Orphanet J Rare Dis. 2017 May 31;12(1):106
pubmed: 28569181
J Immunol. 2002 Oct 1;169(7):3581-8
pubmed: 12244148
J Allergy Clin Immunol. 2012 Feb;129(2):501-9, 509.e1-5
pubmed: 21962992
Trends Biotechnol. 2015 Jan;33(1):27-34
pubmed: 25488117
Nat Rev Immunol. 2010 Jun;10(6):387-402
pubmed: 20467426
J Leukoc Biol. 2001 Mar;69(3):373-80
pubmed: 11261783
Immunity. 2013 Feb 21;38(2):336-48
pubmed: 23352235
Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):
pubmed: 21068150
Arterioscler Thromb Vasc Biol. 2016 May;36(5):855-63
pubmed: 27013611
Haematologica. 2008 Jan;93(1):83-9
pubmed: 18166789
Cancer Immunol Immunother. 1997 Nov-Dec;45(3-4):146-8
pubmed: 9435859
Blood. 2003 May 15;101(10):3933-9
pubmed: 12522008
Science. 2006 Aug 4;313(5787):670-3
pubmed: 16888140
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5336-41
pubmed: 12697896
J Clin Invest. 2005 Oct;115(10):2914-23
pubmed: 16167082
Blood Adv. 2018 Nov 13;2(21):2904-2916
pubmed: 30396910
Haematologica. 2012 Dec;97(12):1855-63
pubmed: 22733016
Blood. 2014 Jan 16;123(3):317-25
pubmed: 24227821
Appl Microbiol Biotechnol. 2015 Dec;99(24):10467-80
pubmed: 26373723
Clin Exp Vaccine Res. 2014 Jul;3(2):113-6
pubmed: 25003083
Vaccine. 2011 Dec 9;30(1):42-50
pubmed: 22064264
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8965-70
pubmed: 17502612
Thromb Haemost. 2006 Sep;96(3):309-16
pubmed: 16953272
Blood. 2009 Apr 16;113(16):3716-25
pubmed: 19018092