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Ligand-binding renders the 160 kDa Trypanosoma cruzi complement regulatory protein susceptible to proteolytic cleavage.
- Source :
-
Microbial pathogenesis [Microb Pathog] 1996 Oct; Vol. 21 (4), pp. 235-48. - Publication Year :
- 1996
-
Abstract
- It has been previously shown that a surface complement regulatory protein (CRP) of Trypanosoma cruzi trypomastigotes binds human complement components C3b and C4b, and inhibits C3 convertase formation, thus contributing to the resistance of the bloodstage parasites to complement-mediated lysis. The blood stage parasites rapidly and spontaneously release a limited set of membrane glycoproteins, including CRP, and the modulation of release of CRP following ligand binding was investigated. Incubation of the parasites with C3b results in the release of CRP at a reduced apparent molecular mass. To determine if proteolytic processing was responsible for the reduction in apparent molecular mass of the released CRP, the proteolytic activity present in trypomastigote membrane preparations was examined. In addition to a well described cysteine protease, a novel 75 kDa protease was identified in tissue culture-derived trypomastigotes and axenically-derived metacyclic trypomastigotes membrane preparations. This protease was inhibited by aprotinin and leupeptin, but not L-trans-epoxysuccinyl-leucylamide-(4-guanidinobutane), N-[N-L-3-transcarboxyirane-2-carbonyl-L-leucinyl]-agmatine (E64). Treatment of the parasites with protease inhibitors did not affect spontaneous shedding of proteins, however, protease inhibitors abrogated the effect of C3b-binding on CRP degradation. These results indicate that binding of C3b to the CRP renders the CRP susceptible to cleavage by a parasite protease, possibly as a means of removing the CRP-C3b from the parasite surface. This process may represent an additional immune evasion mechanism which allows the parasite to avoid both complement-mediated lysis and clearance.
- Subjects :
- Animals
Cell Membrane enzymology
Complement Inactivator Proteins drug effects
Gene Expression Regulation, Enzymologic
Humans
Ligands
Membrane Glycoproteins drug effects
Mice
Mice, Inbred BALB C
Protease Inhibitors pharmacology
Protein Binding
Protozoan Proteins drug effects
Trypanosoma cruzi enzymology
Trypanosoma cruzi immunology
Complement C3b metabolism
Complement Inactivator Proteins metabolism
Endopeptidases metabolism
Membrane Glycoproteins metabolism
Protozoan Proteins metabolism
Trypanosoma cruzi metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0882-4010
- Volume :
- 21
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Microbial pathogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 8905613
- Full Text :
- https://doi.org/10.1006/mpat.1996.0058