A dominant role for extracellular glutathione S-transferase from Onchocerca volvulus is the production of prostaglandin D2

Abstract

The extracellular glutathione S-transferase from the filarial parasite Onchocerca volvulus (Ov-GST1) is a glutathione-dependent prostaglandin D synthase. Ov-GST1, located in the outer hypodermal lamellae and in parts of the cuticle, produces prostaglandin D(2) directly at the parasite-host interface. Ov-GST1 therefore has the potential to participate in the modulation of the host immune response by contributing to the production of prostanoids; this supports the predominant hypothesis that parasite-derived eicosanoids influence host inflammatory and immune cells.

FIG. 1.

PGD synthase activity of rOv-GST1. The PGD synthase activity was measured in a coupled assay using ovine COX-1 and arachidonic acid as the substrate. PG synthesis was performed for 2 min in the presence of 12 (red) or 2.4 μg (blue) of rOv-GST1 and in the absence of rOv-GST1 (black). The HPLC-ESI-MS chromatogram shows the major PG products. RT, retention time; OD₂₁₄, optical density at 214 nm.

FIG. 2.

Analysis of concentration-dependent PGD₂ formation by rOv-GST1. Isomerase activity of rOv-GST1 was determined in a coupled assay with COX-1 and arachidonic acid (a) and in a direct assay using PGH₂ at a constant concentration of 40 μM (b). While PGF_2α and PGE₂ are breakup products of PGH₂, PGD₂ is formed in a concentration-dependent manner by increasing concentrations of rOv-GST1, indicating the specific isomerization of PGH₂ to PGD_2.