Schistosoma japonicum cathepsin D aspartic protease cleaves human IgG and other serum components

Abstract

Recombinant cathepsin D aspartic protease of Schistosoma japonicum cleaved human IgG in vitro in a time and dose-dependent manner. Optimal cleavage was seen at pH 3.6-4.5; modest cleavage remained at pH 5.0, and no cleavage was detected above pH 5.0. Amino terminal sequencing of the major cleavage fragments of human IgG identified a Fab fragment from the VH1 domain, and 2 cleavage sites in the CH2 domain below the hinge region. The P1 and P1' residues at the 2 CH2 cleavage sites were Phe254-Leu255 and Leu325-Thr326, indicating a preference by the schistosome protease for bulky hydrophobic residues flanking the scissile bond. No cleavage of the immunoglobulin light chain was detected. In addition, the recombinant schistosome protease indiscriminately degraded the human serum proteins complement C3 and serum albumin into numerous small fragments. These results demonstrate specific cleavage of human IgG by the recombinant schistosome aspartic protease, and highlight the broad range digestive specificity of the enzyme which may play a role in the degradation of host serum proteins ingested as part of the schistosome bloodmeal.

Immune Responses in Hookworm Infections

“…Computer modeling of this protein (AcASP1) predicted that it would cleave canine hemoglobin more efficiently than it cleaved human hemoglobin (16). Recently, recombinant Schistosoma japonicum aspartic protease was shown to cleave Igs at the hinge region as well as the complement protein C3 in vitro (146). While an immunoevasive role has not been investigated for hookworm aspartic proteases, it is probable that they perform multiple functions in vivo.…”

Lipid core peptide targeting the cathepsin D hemoglobinase ofSchistosoma mansonias a component of a schistosomiasis vaccine

“…11 In S. japonicum CatD has previously been localized to the cecal lumen, gastrodermis and the tegument. 7,40,41 In S. mansoni however, the catD mRNA has been identified in gastrodermal tissue 42 but has not been immunolocalized until now.…”

“…[7][8][9] Transcripts for CatD are present in all stages of the parasite and the enzyme is also capable of digesting immunoglobulin and serum components such as albumin. [10][11][12] Vaccination with recombinant forms of S. japonicum CatD in the mouse model of schistosomiasis achieved significant reductions in total worm burden across numerous trials. 13 RNA interference targeting the gene encoding S. mansoni CatD resulted in a lethal phenotype (growth retardation) and the reduction in the ability of the parasite to effectively digest Hb in vitro.…”

Derived Products of Helminth in the Treatment of Inflammation, Allergic Reactions and Anaphylaxis

“…In addition, S. mansoni schitosomula produces a trypsine-like proteinase or aminopeptidase that cleave Fab fragment when Fc receptor of the worm binds IgG (Auriault et al, 1981). Recombinant schistosome aspartic proteases from S. japonicum cleave specifically human IgG, suggesting that these proteases may play a role in the degradation of host serum proteins ingested as part of the schistosome bloodmeal (Verity et al, 2001). …”