Factor VII-activating protease (FSAP) removes nucleosomes from apoptotic cells and is inhibited by C1-inhibitor (C1Inh) and 2-antiplasmin (AP).

The authors compared FSAP activation in the presence of apoptotic vs. non-apoptotic cells. FSAP in plasma was found to be activated upon incubation with apoptotic cells as evidenced by appearance of two-chain FSAP on western blots. No FSAP activation was observed upon incubation of plasma with living cells. FSAP activation by apoptotic cells was also indicated by complex formation of FSAP with C1Inh and AP, whereas no such complexes could be detected after incubation with living cells.

Moreover, the authors asked, whether a similar mechanism can also be expected in vivo and they analysed plasmas from cases of sepsis, during which the formation of apoptotic cells is a hallmark-They found elevated levels of FSAP/C1Inh complexes in plasma of baboons with lethal sepsis and in plasmas from 8 out of 16 patients suffering from severe sepsis.

In conclusion the authors demonstrate that FSAP is activated upon contact with apoptotic cells and forms complexes with C1Inh and AP. They sugest, that determination of complexes between FSAP and C1Inh or AP in plasma is  a tool to study FSAP activation in vivo.

Title:
Factor VII-activating protease is activated in sepsis

Authors and Source:
S Zeerleder, I Bulder, F Stephan, M de Kruif, J Hoogerwerf, T van der Poll, L Aarden
ISTH 2009: PP-TH-153