Ecotin, a microbial inhibitor of serine proteases, blocks multiple complement dependent and independent microbicidal activities of human serum
Fig 6
Ecotin is shown to inhibit LP- and AP-activation in human, and LP-activation in mouse and rat serum.
C3-deposition on mannan-coated plates from dilute sera was measured as a function of inhibitor-concentration. All four tested ecotin orthologs are equally potent inhibitors of LP-activation in 50-fold diluted NHS. Their effects are comparable to that of our previously evolved selective MASP-2 inhibitor, SGMI-2. (A) E. coli ecotin inhibits the LP in analogous tests using 60-fold diluted pooled sera of C57BL/6 and BALB/c mice. (B), and 60-fold diluted serum of Wistar rat (C). IC50 values for human and rodent serum are listed in (D) and (E), respectively. In the about 10-fold more concentrate, 6-fold diluted NHS used for the alternative pathway inhibition tests, 10 μM of the ecotin orthologs provide ortholog-specific, but significant inhibition, L. major ecotin being the most potent one (F). Symbols represent the average of at least two measurements. Error bars represent the SEM.