Enzymatic effect of hypodermin A, a parasite protease, on bovine lymphocyte membrane antigens.

The protease hypodermin A (HA) is produced by the parasitic warble-fly larva and is implicated in the modulation of the bovine immune system. This study examines the effect of this enzyme on the cell surface markers of bovine lymphocytes. HA interfered with the binding of all anti-lymphocyte receptor antibodies tested. Anti-BoCD2 and CD5 staining was completely abolished. But the mean fluorescence intensity (MFI) only was diminished for antibodies against BoCD4, CD8 and CD18. On the contrary, the MFI for anti-MHC Cl I molecules staining was increased. This effect of HA began as early as one h, and was reversed by removal of HA. Heating or PMSF treatment, which both inhibit protease activity, abolished the action of HA on the surface antigens. The HA concentrations (100 micrograms/ml) needed to alter antibody binding were similar to those that inhibited phytohaemagglutinin (PHA)-induced proliferation. These results show that enzymatic activity of HA on lymphocyte surface markers may be implicated in the inhibition of lymphocyte proliferation.

Effect of the parasite enzyme, hypodermin A, on bovine lymphocyte proliferation and interleukin-2 production via the prostaglandin pathway.

The immune function of cattle infected with a primary infestation of Hypoderma lineatum is impaired during the first instar migration of the larvae. Hypodermin A (HA) is an enzyme secreted by the larvae that is implicated in immunosuppression. The response of bovine peripheral blood mononuclear cells (PBMC) to HA was examined in this study. HA blocked their proliferation in response to phytohaemagglutinin (PHA) and its effect was enhanced when cells were preincubated with HA before activation. This suggests that HA affects the lymphocyte commitment to blastogenesis during the early stages of their activation. HA also markly reduced the production of interleukin-2 (IL-2) in PHA-stimulated bovine PBMC cultures. Furthermore, indomethacin, which inhibits prostaglandin (PG) synthesis, blocked the immunosuppressive effect of HA on the PBMC proliferative response. The concentration of PGE2 in medium of PBMC or PMA-stimulated monocyte cultures was increased by incubation with HA. Thus, the HA appeared to act by reducing IL-2 production via a prostaglandin-dependent pathway.