Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.

Factor X (FX), a plasma glycoprotein playing a central role in coagulation has a long circulatory half-life compared to closely related coagulation factors. The activation peptide of FX has been shown to influence its clearance with two N-glycans as key determinants of FX's relatively long surv...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mohamad Kurdi, Ghislaine Cherel, Peter J Lenting, Cécile V Denis, Olivier D Christophe
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/998d4d7e17784cbd9818af40362ee833
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:998d4d7e17784cbd9818af40362ee833
record_format	dspace
spelling	oai:doaj.org-article:998d4d7e17784cbd9818af40362ee8332021-11-18T08:14:14ZCoagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.1932-620310.1371/journal.pone.0045111https://doaj.org/article/998d4d7e17784cbd9818af40362ee8332012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049768/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Factor X (FX), a plasma glycoprotein playing a central role in coagulation has a long circulatory half-life compared to closely related coagulation factors. The activation peptide of FX has been shown to influence its clearance with two N-glycans as key determinants of FX's relatively long survival. To decipher FX clearance mechanism, organ biodistribution and cellular interactions of human plasma FX (pd-FX), recombinant FX (rFX), N-deglycosylated FX (N-degly-FX) and recombinant FX mutated at both N-glycosylation sites (rFX(N181A-N191A)) were evaluated. Biodistribution analysis of (125)I-labelled FX proteins after administration to mice revealed liver as major target organ for all FX variants. Liver tissue sections analysis showed an interaction of pd-FX and N-degly-FX to different cell types. These findings were confirmed in cell binding studies revealing that FX and FX without N-glycans interact with macrophages and hepatocytes, respectively. N-degly-FX appeared to be degraded in hepatocytes while interestingly pd-FX was not by macrophages. Furthermore, the chemical inactivation of macrophages by gadolinium chloride resulted in a significant decrease of circulating pd-FX into mice and not of N-degly-FX. Altogether our data lead to the conclusion that FX interaction with macrophages through its N-glycans protects it from a rapid clearance explaining its relatively long circulatory half-life.Mohamad KurdiGhislaine CherelPeter J LentingCécile V DenisOlivier D ChristophePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45111 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohamad Kurdi Ghislaine Cherel Peter J Lenting Cécile V Denis Olivier D Christophe Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.
description	Factor X (FX), a plasma glycoprotein playing a central role in coagulation has a long circulatory half-life compared to closely related coagulation factors. The activation peptide of FX has been shown to influence its clearance with two N-glycans as key determinants of FX's relatively long survival. To decipher FX clearance mechanism, organ biodistribution and cellular interactions of human plasma FX (pd-FX), recombinant FX (rFX), N-deglycosylated FX (N-degly-FX) and recombinant FX mutated at both N-glycosylation sites (rFX(N181A-N191A)) were evaluated. Biodistribution analysis of (125)I-labelled FX proteins after administration to mice revealed liver as major target organ for all FX variants. Liver tissue sections analysis showed an interaction of pd-FX and N-degly-FX to different cell types. These findings were confirmed in cell binding studies revealing that FX and FX without N-glycans interact with macrophages and hepatocytes, respectively. N-degly-FX appeared to be degraded in hepatocytes while interestingly pd-FX was not by macrophages. Furthermore, the chemical inactivation of macrophages by gadolinium chloride resulted in a significant decrease of circulating pd-FX into mice and not of N-degly-FX. Altogether our data lead to the conclusion that FX interaction with macrophages through its N-glycans protects it from a rapid clearance explaining its relatively long circulatory half-life.
format	article
author	Mohamad Kurdi Ghislaine Cherel Peter J Lenting Cécile V Denis Olivier D Christophe
author_facet	Mohamad Kurdi Ghislaine Cherel Peter J Lenting Cécile V Denis Olivier D Christophe
author_sort	Mohamad Kurdi
title	Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.
title_short	Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.
title_full	Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.
title_fullStr	Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.
title_full_unstemmed	Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.
title_sort	coagulation factor x interaction with macrophages through its n-glycans protects it from a rapid clearance.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/998d4d7e17784cbd9818af40362ee833
work_keys_str_mv	AT mohamadkurdi coagulationfactorxinteractionwithmacrophagesthroughitsnglycansprotectsitfromarapidclearance AT ghislainecherel coagulationfactorxinteractionwithmacrophagesthroughitsnglycansprotectsitfromarapidclearance AT peterjlenting coagulationfactorxinteractionwithmacrophagesthroughitsnglycansprotectsitfromarapidclearance AT cecilevdenis coagulationfactorxinteractionwithmacrophagesthroughitsnglycansprotectsitfromarapidclearance AT olivierdchristophe coagulationfactorxinteractionwithmacrophagesthroughitsnglycansprotectsitfromarapidclearance
_version_	1718422059585896448

Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance.

Ejemplares similares