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PMID: 9199414 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The tumor necrosis factor alpha-stimulating region of galactose-inhibitable lectin of Entamoeba histolytica activates gamma interferon-primed macrophages for amebicidal activity mediated by nitric oxide.

Infection and immunity ·Vol. 65 ·No. 7 ·1997-07-00 ·Pages 2522-7

Séguin R, Mann BJ, Keller K, Chadee K

Abstract

Entamoeba histolytica adheres via galactose-lectin (Gal-lectin) to human colonic mucins and intestinal epithelial cells as a prerequisite to amebic invasion. Native Gal-lectin is a protective antigen in the gerbil model of amebiasis. Amino acids 596 to 1082 of Gal-lectin mediate E. histolytica adherence to target cells and stimulate tumor necrosis factor alpha (TNF-alpha) production by naive murine bone marrow macrophages (BMM). Resistance to amebiasis requires an effective cell-mediated immune response against E. histolytica trophozoites mediated by nitric oxide (NO) released from activated macrophages. Herein, we determine whether the TNF-alpha-stimulating region of Gal-lectin can activate gamma interferon (IFN-gamma)-primed BMM for NO production and amebicidal activity. Native Gal-lectin (100 to 500 ng/ml) stimulated TNF-alpha and inducible nitric oxide synthase (iNOS) mRNA expression in IFN-gamma-primed BMM as did lipopolysaccharide (100 ng/ml). Primed BMM produced TNF-alpha and NO in response to Gal-lectin in a dose-dependent manner. Antilectin monoclonal antibody IG7, which recognizes a domain (amino acids 596 to 818) of the TNF-alpha mRNA-stimulating region of Gal-lectin, specifically inhibited TNF-alpha and iNOS mRNA induction and TNF-alpha and NO production by primed BMM in response to Gal-lectin (100 ng/ml). Simultaneous treatment of BMM with IFN-gamma and Gal-lectin (100 ng/ml) activated the cells to kill E. histolytica trophozoites, whereas IFN-gamma treatment alone had no effect. In the presence of monoclonal antibody 1G7 or aminoguanidine (an iNOS inhibitor), NO production and amebicidal activity were inhibited >80%. These results suggest that the TNF-alpha-stimulating region of native Gal-lectin is a potent stimulus of IFN-gamma-primed BMM for NO production, which is essential for host defense against amebiasis.

MeSH Terms
Animals Antibodies, Monoclonal Bone Marrow/immunology Entamoeba histolytica/immunology Entamoebiasis/immunology Female In Vitro Techniques Interferon-gamma/pharmacology Lectins/pharmacology Macrophages/immunology Mice Mice, Inbred BALB C Nitric Oxide/biosynthesis,physiology Nitric Oxide Synthase/metabolism Protozoan Proteins/pharmacology RNA, Messenger/analysis Tumor Necrosis Factor-alpha/biosynthesis,genetics
Chemicals
Antibodies, Monoclonal Lectins Protozoan Proteins RNA, Messenger Tumor Necrosis Factor-alpha N-acetylgalactosamine inhibitable lectin 35-kDa subunit, Entamoeba histolytica Nitric Oxide Interferon-gamma Nitric Oxide Synthase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Séguin R
Institute of Parasitology of McGill University, Macdonald Campus, Quebec, Canada.
Mann B J
Keller K
Chadee K
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.65.7.2522-2527.1997
Published
1997-07-00
Pages
2522-7
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC175356
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.65.7.2522-2527.1997 PMC Full Text View journal details
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