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Oxygen-independent killing by alveolar macrophages

We have found that normal alveolar macrophages can kill an intracellular parasite by a mechanism that does not involve toxic metabolites of oxygen. We studied the interaction between Toxoplasma gondii and rat alveolar macrophages in vitro. We were interested in Toxoplasma because it causes pneumonia...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1986
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2188110/
https://www.ncbi.nlm.nih.gov/pubmed/3009680
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description We have found that normal alveolar macrophages can kill an intracellular parasite by a mechanism that does not involve toxic metabolites of oxygen. We studied the interaction between Toxoplasma gondii and rat alveolar macrophages in vitro. We were interested in Toxoplasma because it causes pneumonia in immunosuppressed patients but not in healthy individuals, and we chose the rat because it resembles immunocompetent human subjects in being resistant to T. gondii. Resident rat alveolar macrophages could kill large numbers of T. gondii. This occurred without a respiratory burst as judged by intracellular reduction of nitroblue tetrazolium and quantitative release of superoxide. Furthermore, scavengers of toxic oxygen metabolites had no effect on the toxoplasmacidal activity of the alveolar macrophages, nor did prior exhaustion of their respiratory burst with PMA. Whereas acid pH (e.g., 4.5-6.0) rapidly kills extracellular T. gondii, raising of the intralysosomal acid pH of rat alveolar macrophages by incubating them with weak bases did not inhibit their ability to kill T. gondii. Killing of Toxoplasma occurred within 1 h of initial exposure to the alveolar macrophages. However, there was no evidence that killing preceded ingestion; Toxoplasma attached to the surface of the cell appeared viable, and when phagocytosis was blocked with sodium fluoride the organisms survived. These results indicate that rat alveolar macrophages possess a powerful nonoxidative microbicidal mechanism, which is distinct from acidification of the phagolysosome but which probably involves phagosome formation. This mechanism may be clinically relevant, for we have recently observed that human alveolar macrophages also kill T. gondii by an oxygen- independent process.
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spelling pubmed-21881102008-04-17 Oxygen-independent killing by alveolar macrophages J Exp Med Articles We have found that normal alveolar macrophages can kill an intracellular parasite by a mechanism that does not involve toxic metabolites of oxygen. We studied the interaction between Toxoplasma gondii and rat alveolar macrophages in vitro. We were interested in Toxoplasma because it causes pneumonia in immunosuppressed patients but not in healthy individuals, and we chose the rat because it resembles immunocompetent human subjects in being resistant to T. gondii. Resident rat alveolar macrophages could kill large numbers of T. gondii. This occurred without a respiratory burst as judged by intracellular reduction of nitroblue tetrazolium and quantitative release of superoxide. Furthermore, scavengers of toxic oxygen metabolites had no effect on the toxoplasmacidal activity of the alveolar macrophages, nor did prior exhaustion of their respiratory burst with PMA. Whereas acid pH (e.g., 4.5-6.0) rapidly kills extracellular T. gondii, raising of the intralysosomal acid pH of rat alveolar macrophages by incubating them with weak bases did not inhibit their ability to kill T. gondii. Killing of Toxoplasma occurred within 1 h of initial exposure to the alveolar macrophages. However, there was no evidence that killing preceded ingestion; Toxoplasma attached to the surface of the cell appeared viable, and when phagocytosis was blocked with sodium fluoride the organisms survived. These results indicate that rat alveolar macrophages possess a powerful nonoxidative microbicidal mechanism, which is distinct from acidification of the phagolysosome but which probably involves phagosome formation. This mechanism may be clinically relevant, for we have recently observed that human alveolar macrophages also kill T. gondii by an oxygen- independent process. The Rockefeller University Press 1986-05-01 /pmc/articles/PMC2188110/ /pubmed/3009680 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Oxygen-independent killing by alveolar macrophages
title Oxygen-independent killing by alveolar macrophages
title_full Oxygen-independent killing by alveolar macrophages
title_fullStr Oxygen-independent killing by alveolar macrophages
title_full_unstemmed Oxygen-independent killing by alveolar macrophages
title_short Oxygen-independent killing by alveolar macrophages
title_sort oxygen-independent killing by alveolar macrophages
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2188110/
https://www.ncbi.nlm.nih.gov/pubmed/3009680