Specific inhibition of Trypanosoma cruzi neuraminidase by the human plasma glycoprotein "cruzin".
Plasma of normal human individuals was shown to contain an inhibitor of Trypanosoma cruzi neuraminidase (NAase; acylneuraminyl hydrolase, sialidase, EC 3.2.1.18). The inhibitor has been purified to homogeneity by PEG precipitation, CM Affi-Gel Blue Sepharose chromatography, and gel filtration. The purified preparation inhibits T. cruzi NAase at a concentration as low as 10(-9) M and has no effect at concentrations at least 100 times higher on any of the other NAases tested, including those from influenza virus, the closely related trypanosome Trypanosoma rangeli, and mammalian NAases. The inhibitor is unique in that it prevents T. cruzi desialylation of intact mammalian cells but does not prevent desialylation of soluble glycoconjugates. In addition, the isolated material is effective in inhibiting the T. cruzi NAase whether the enzyme is on the parasite outer membrane or in solution. Molecular characterization indicates that the inhibitor is a glycoprotein with a Mr of 246,000 +/- 20,000 composed of subunits of Mr 28,000 +/- 2000. Its plasma concentration is at least 60 micrograms/ml. The mechanism of action has not been fully elucidated, but it appears to be noncompetitive. Attempts to match the isolated NAase inhibitor with known plasma glycoproteins have not been successful. In view of this and of the specificity of the inhibitor for T. cruzi, we have named the inhibitor "cruzin." This finding suggests a different approach in investigating the role that NAase plays in host-parasite interaction.
D000818:Animals; D000890:Anti-Infective Agents; D001798:Blood Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D002241:Carbohydrates / Q000032:analysis; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D013045:Species Specificity; D014349:Trypanosoma cruzi / Q000201:enzymology*
D000890:Anti-Infective Agents; D001798:Blood Proteins; D002241:Carbohydrates; D046911:Macromolecular Substances; D009439:Neuraminidase