| Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy loss. | |
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MedLine Citation:
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PMID: 16537414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Stimulation of CD1d-restricted semiinvariant natural killer T cells by using the CD1d ligand alpha-galactosylceramide (alphaGalCer) induces pregnancy loss in mice through an ill-defined mechanism involving TNF, IFN-gamma, and perforin. In this article, we demonstrate that during early gestation, alphaGalCer efficiently induced pregnancy loss in C57BL/6J and BALB/cJ mice in a perforin-dependent manner. In contrast, during midgestation perforin was no longer required for pregnancy loss. Concomitant with the loss of a perforin requirement at midgestation was the emergence of strain-dependent variations in susceptibility to alphaGalCer-induced pregnancy loss. Whereas pregnant C57BL/6J mice remained susceptible to alphaGalCer at midgestation, pregnant BALB/cJ mice were resistant to its effects. Pregnancy loss during midgestation was correlated with dramatically higher serum cytokine levels, including TNF and IL-2, in the susceptible C57BL/6J strain compared with the resistant BALB/cJ strain. Thus, the stage of gestation defined two distinct mechanisms of pregnancy loss: a perforin-dependent mechanism operating at early gestation and a perforin-independent, cytokine-dominated mechanism operating after midgestation. |
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Authors:
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Jonathan E Boyson; Nisha Nagarkatti; Leena Nizam; Mark A Exley; Jack L Strominger |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-03-14 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 103 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-03-22 Completed Date: 2006-05-11 Revised Date: 2012-03-07 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 4580-5 Citation Subset: IM |
Affiliation:
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Division of Transplantation Surgery and Immunology, Department of Surgery, University of Vermont College of Medicine, Burlington, VT 05405, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD1 / analysis* Antigens, CD1d Female Galactosylceramides / pharmacology Interleukin-2 / blood Killer Cells, Natural / drug effects, immunology* Ligands Membrane Glycoproteins / metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Perforin Pore Forming Cytotoxic Proteins Pregnancy Premature Birth / genetics, immunology*, pathology T-Lymphocytes / drug effects, immunology* Tumor Necrosis Factor-alpha / analysis |
| Grant Support | |
ID/Acronym/Agency:
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AI 053330/AI/NIAID NIH HHS; F32 HD008515-01/HD/NICHD NIH HHS; F32 HD008515-02/HD/NICHD NIH HHS; F32 HD008515-03/HD/NICHD NIH HHS; R01 AI067897-01A2/AI/NIAID NIH HHS; R01 AI067897-02/AI/NIAID NIH HHS; R01 AI067897-03/AI/NIAID NIH HHS; R01 AI067897-04/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD1; 0/Antigens, CD1d; 0/Galactosylceramides; 0/Interleukin-2; 0/Ligands; 0/Membrane Glycoproteins; 0/Pore Forming Cytotoxic Proteins; 0/Tumor Necrosis Factor-alpha; 0/alpha-galactosylceramide; 126465-35-8/Perforin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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