Coagulation Factor X Interaction with Macrophages through Its N-Glycans Protects It from a Rapid ClearanceReportar como inadecuado




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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 rFXN181A–N191A were evaluated. Biodistribution analysis of 125I-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.



Autor: Mohamad Kurdi, Ghislaine Cherel, Peter J. Lenting, Cécile V. Denis, Olivier D. Christophe

Fuente: http://plos.srce.hr/



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