Proteolytic cleavage of immunoglobulin by enzymes released by Fasciola hepatica

Abstract

Immature Fasciola hepatica release a papain or cathepsin B-like proteolytic enzyme which cleaves immunoglobulins (Ig) of mouse, rat, rabbit and sheep in vitro. Mouse IgG and IgM molecules are both susceptible to cleavage as is hemoglobin. Whether single or multiple proteases are responsible for Ig cleavage is unknown. The proteolytic activity of secreted enzyme(s) is optimal at pH 3.5-4.5, but activity is also present at pH 7. Proteolysis is enhanced in the presence of 5 mM dithiothreitol or 100 mM cysteine. Based on studies with protease inhibitors, the F. hepatica enzyme activity has been identified as a thiol protease. It is destroyed by heating at 56 degrees C for 1 h, but retains activity after storage at -20 degrees C for 7 days. Whether inhibition of the proteolytic activity increases the susceptibility of F. hepatica immature worm to any extant immune effector mechanisms in hosts remains to be determined.