Oxygen-independent killing by alveolar macrophages
| Autor: | S D Sharma, Jack S. Remington, J R Catterall |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Cytotoxicity
Immunologic Phagocytosis Immunology In Vitro Techniques Biology Phagolysosome Ammonium Chloride Microbiology Methylamines Mice Superoxides parasitic diseases medicine Animals Immunology and Allergy Macrophage Peritoneal Cavity Cells Cultured Phagosome Lung Macrophages Toxoplasma gondii Articles biology.organism_classification Rats Respiratory burst Oxygen Pulmonary Alveoli medicine.anatomical_structure Rats Inbred Lew Tetradecanoylphorbol Acetate Pulmonary alveolus Lysosomes Toxoplasma |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.163.5.1113 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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