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|dc.title||High-affinity LPS binding domain(s) in recombinant factor C of a horseshoe crab neutralizes LPS-induced lethality|
|dc.contributor.author||Soon Tan, N.|
|dc.identifier.citation||Soon Tan, N.,Ho, B.,Ding, J.L. (2000). High-affinity LPS binding domain(s) in recombinant factor C of a horseshoe crab neutralizes LPS-induced lethality. FASEB Journal 14 (7) : 859-870. ScholarBank@NUS Repository.|
|dc.description.abstract||SSCrFCES is a biologically active, recombinant fragment of factor C, which is the endotoxin-sensitive serine protease of the LAL coagulation cascade. The ~38 kDa protein represents the LPS binding domain of factor C. A novel secretory signal directs the secretion of SSCrFCES into the culture supernatant of Drosophila cells, and hence it is readily purified. By differential ultrafiltration followed by preparative isoelectric membrane electrophoresis, SSCrFCES was purified as an isoelectrically homogeneous and stable monomeric protein. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. SSCrFCES exhibits high positive cooperativity of binding to two or three lipid A molecules, with a Hill's coefficient of 2.2. The 50% endotoxin- neutralizing concentration of SSCrFCES against 200 EU of endotoxin is ~0.069 μM, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as little as 1 μM of SSCrFCES inhibits the LPS-induced secretion of hTNF-α and hIL-8 by THP-1 and human peripheral blood mononuclear cells with greater potency than polymyxin B. SSCrFCES is noncytotoxic, with a clearance rate of 4.7 ml/min. The L.D.90 of SSCrFCES for LPS lethality is achieved at 2 μM. These results demonstrate the endotoxin-neutralizing capability of SSCrFCES in vitro and in vivo and its potential use for the treatment of endotoxin-induced septic shock.|
|dc.subject||Endotoxin binding and neutralization|
|dc.subject||Novel secretory signal|
|Appears in Collections:||Staff Publications|
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