Endothelial Cells are Activated by Cytokine Treatment to Kill an Intravascular Parasite, Schistosoma mansoni, through the Production of Nitric Oxide

Like many pathogens that undergo an intravascular stage of development, larvae of the helminth parasite Schistosoma mansoni migrate through the blood vessels, where they are in close contact with endothelial cells. In vitro exposure of murine endothelial cells to various cytokines (interferon γ, tum...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-02, Vol.91 (3), p.999-1003
Main Authors: Oswald, Isabelle P., Eltoum, Isam, Wynn, Thomas A., Schwartz, Bertrand, Caspar, Patricia, Paulin, Denise, Sher, Alan, James, Stephanie L.
Format: Article
Language:English
Subjects:
Amino Acid Oxidoreductases - genetics
Analysis of the immune response. Humoral and cellular immunity
Animals
Arginine - analogs & derivatives
Arginine - pharmacology
Base Sequence
Biological and medical sciences
Cellular biology
Cytokines
Cytokines - pharmacology
Cytotoxicity, Immunologic - drug effects
DNA Probes - genetics
Endothelial cells
Endothelium, Vascular - immunology
Endothelium, Vascular - metabolism
Endothelium, Vascular - parasitology
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunity (Disease)
Immunity, Cellular - drug effects
Immunobiology
In Vitro Techniques
Infections
Larvae
Larval development
Lung - blood supply
Lung - pathology
Lungs
Macrophages
Medical research
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Nitric Oxide - biosynthesis
Nitric Oxide Synthase
Organs and cells involved in the immune response
Parasites
RNA, Messenger - genetics
Schistosoma mansoni
Schistosoma mansoni - immunology
Schistosomiasis mansoni - immunology
Schistosomiasis mansoni - pathology
Schistosomiasis mansoni - prevention & control
Schistosomula
Vaccination
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Summary:Like many pathogens that undergo an intravascular stage of development, larvae of the helminth parasite Schistosoma mansoni migrate through the blood vessels, where they are in close contact with endothelial cells. In vitro exposure of murine endothelial cells to various cytokines (interferon γ, tumor necrosis factor α, and interleukin 1α or 1β) resulted in their activation to kill schistosomula through an arginine-dependent mechanism involving production of nitric oxide (NO). Cytokine-treated endothelial cells showed increased expression of mRNA for the inducible form of the NO synthase, and both NO production and larval killing were suppressed by treatment with competitive inhibitors. The effector function of cytokine-treated endothelial cells was similar to that of activated inflammatory tissue macrophages, although activation appeared to be differentially regulated in these two cell types. Activated endothelial cells killed older (18-day) forms of the parasite, such as those currently thought to be a primary target of immune elimination in the lungs of mice previously vaccinated with radiation-attenuated cercariae, as well as newly transformed larvae. In C57BL/6 mice, which become resistant to S. mansoni infection as a result of vaccination with irradiated cercariae, endothelial cell morphology characteristic of activation was observed in the lung by 1-2 weeks after challenge infection. Similar endothelial cell changes were absent in P-strain mice, which do not become resistant as a result of vaccination. Together, these observations indicate that endothelial cells, not traditionally considered to be part of the immune system, may play an important role in immunity to S. mansoni and, by means of NO-dependent killing, could serve as effectors of resistance to other intravascular pathogens.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.3.999