| First Author | Kurdi M | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 9 | Pages | e45111 |
| PubMed ID | 23049768 | Mgi Jnum | J:191951 |
| Mgi Id | MGI:5463685 | Doi | 10.1371/journal.pone.0045111 |
| Citation | Kurdi M, et al. (2012) Coagulation factor X interaction with macrophages through its N-glycans protects it from a rapid clearance. PLoS One 7(9):e45111 |
| abstractText | 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. |
