Surface Zn-proteinase as a molecule for defense of Leishmania mexicana amazonensis promastigotes against cytolysis inside macrophage phagolysosomes.

Infection and Immunity
M B SeayG Chaudhuri

Abstract

The role of the surface membrane Zn-proteinase in protecting the cellular integrity of the macrophage parasite Leishmania mexicana amazonensis from intraphagolysosomal cytolysis was studied. These cells lose their infectivity to host macrophages after prolonged cultivation in axenic growth medium. The virulent and attenuated variants of the parasite cells were cloned. Failure of these attenuated parasite cells to survive inside macrophage phagolysosomes is associated with 20- to 50-fold reduction in the expression of surface gp63 protein. In situ inhibition of gp63 proteinase activity inside Leishmania-infected macrophage phagolysosomes with targeted delivery of an inhibitor of gp63 proteinase activity, 1,10-phenanthroline, selectively eliminated intracellular Leishmania amastigotes, further suggesting the importance of this proteinase in phagolysosomal survival of the parasite. An upstream sequence (US) of the gp63 gene was cloned in front of the bacterial chloramphenicol acetyltransferase (CAT) gene in plasmid pCATbasic. Transfection of L. mexicana amazonensis cells with this recombinant plasmid showed that expression of the CAT gene from this US is 15- to 20-fold higher in virulent clones than in avirulent clones of the para...Continue Reading

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Citations

Jan 25, 2007·Annals of Tropical Medicine and Parasitology·J Porter-KelleyG Chaudhuri
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Apr 28, 2004·Molecular and Biochemical Parasitology·Chaoqun YaoMary E Wilson
Jun 28, 2005·Molecular and Biochemical Parasitology·Smita MisraGautam Chaudhuri
Dec 11, 2007·Molecular and Biochemical Parasitology·Chia-Hung Christine HsiaoMary E Wilson
Jul 10, 2010·Vaccine·Amir Nejad-Moghaddam, Mohsen Abolhassani

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