Proteases secreted by transforming schistosomula of Schistosoma mansoni promote resistance to killing by complement.
Early events in the transformation of schistosomula of Schistosoma mansoni include shedding of the glycocalyx and conversion of the parasite from sensitive to resistant to complement-mediated killing. This is accompanied by a release of proteolytic activity which occurs at the same rate as the first two phenomena and is also complete within 1 h of culture at 37 degrees C in defined synthetic medium. Two serine proteases, of 28 kDa and a 60 kDa, were purified to homogeneity from the culture medium of transforming schistosomula; the purification steps and the initial characterization of these proteases are reported elsewhere. Both proteases accelerated the release of surface molecules from the schistosomula; however, the effect of the 28-kDa protease was much more pronounced. Qualitative analysis of the material cleaved from the schistosomula by the purified proteases on SDS-PAGE revealed a fragmentation pattern identical with that of the material shed spontaneously from transforming schistosomula. This strongly suggests that the 28-kDa and 60-kDa proteases contribute physiologically to the release of the schistosomular surface molecules including the high Mr glycocalyx. The activity of the two proteases was inhibited by PMSF. Freshly transformed schistosomula treated shortly with the purified 28-kDa protease produced a lower C consumption and became more refractory to C killing. Both consumption and killing were mediated by the alternative pathway of C in the absence of antibodies. These results postulate a role for proteases secreted by transforming schistosomula in the release of schistosomular surface molecules which activate C. This may serve as an escape mechanism from C damage employed by transforming schistosomula.
D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000254:growth & development / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000201:enzymology / Q000276:immunology*
D008565:Membrane Proteins; D010447:Peptide Hydrolases