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PMID: 8618866 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of the galactose-adherence lectin epitopes of Entamoeba histolytica that stimulate tumor necrosis factor-alpha production by macrophages.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 26 ·1995-12-19 ·Pages 12175-9

Séguin R, Mann BJ, Keller K, Chadee K

Abstract

The 170-kDa subunit of the galactose-adherence lectin (Gal-lectin) of Entamoeba histolytica mediates adherence to human colonic mucins and intestinal epithelium as a prerequisite to amebic invasion. The Gal-lectin is an immunodominant molecule and a protective antigen in the gerbil model of amebiasis. Tumor necrosis factor alpha (TNF-alpha) produced by activated macrophages enhances nitric oxide-dependent cytotoxicity in host defense against E. histolytica. The purpose of this study was to identify the Gal-lectin epitopes which stimulate TNF-alpha production by macrophages. Murine bone marrow-derived macrophages (BMMs) exposed to Gal-lectin (100-500 ng/ml) stimulated stable expression of TNF-alpha mRNA (8-fold increase) and TNF-alpha production similar to that of lipopolysaccharide-stimulated cells (100 ng/ml). Polyclonal anti-lectin serum specifically inhibited TNF-alpha mRNA induction in response to the Gal-lectin but not to lipopolysaccharide. Anti-lectin monoclonal antibodies 8C12, H85 and 1G7, which recognize nonoverlapping epitopes of the cysteine-rich region of the 170-kDa heavy subunit, inhibited both amebic adherence to mammalian cells and Gal-lectin-stimulated TNF-alpha mRNA expression by BMMs,but monoclonal antibody 7F4 did neither. As these inhibitory antibodies map to amino acids 596-1082 of the 170-kDa Gal-lectin, our results have identified the functional region that mediates amebic adherence and TNF-alpha mRNA induction in BMMMs; thus, this region of the Gal-lectin is a subunit vaccine candidate.

MeSH Terms
Animals Antibodies, Monoclonal Antigens, Surface/immunology,isolation & purification Blotting, Western Bone Marrow Cells CHO Cells Cell Adhesion Cells, Cultured Cricetinae Entamoeba histolytica/immunology Epitopes/immunology Lectins Macrophages/cytology,drug effects,immunology Membrane Glycoproteins/immunology,isolation & purification,pharmacology Mice Mice, Inbred BALB C Protozoan Proteins/immunology,isolation & purification,pharmacology Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
Antibodies, Monoclonal Antigens, Surface Epitopes Lectins Membrane Glycoproteins Protozoan Proteins Tumor Necrosis Factor-alpha galactose inhibitable adherence protein, Entamoeba histolytica
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Séguin R
Institute of Parasitology of McGill University, Ste. Anne-de-Bellevue, PQ Canada.
Mann B J
Keller K
Chadee K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.26.12175
Published
1995-12-19
Pages
12175-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40319
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.26.12175 PMC Full Text View journal details
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