Mueller, Mathias and Althaus, Roland and Froehlich, Dieter and Frei, Karl and Eugster, Hans Pietro (1999) Reduced antilisterial activity of TNF-deficient bone marrow-derived macrophages is due to impaired superoxide production. EUROPEAN JOURNAL OF IMMUNOLOGY, 29 (10). pp. 3089-3097. ISSN 0014-2980,
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Mice deficient for TNF ligand and receptor type 1 have demonstrated the importance of TNF in the host defense against Listeria monocytogenes. To investigate the particular deficiency of macrophages derived from TNF/lymphotoxin (LT)-alpha(-/-) mice in antilisterial growth control, bone marrow-derived macrophages (BMDM) were used for in vitro infection experiments. After the combined treatment with IFN-gamma and lipopolysaccharide (LPS), production of NO by wild-type (wt) and TNF/LT-alpha(-/-) BMDM was induced to comparable levels, but only wt BMDM controlled L. monocytogenes growth efficiently. Nevertheless, inhibition of NO production led to a remarkable loss of antilisterial activity. This suggests that presence of NO is necessary but not sufficient for L. monocytogenes killing and that elimination of L. monocytogenes requires additional effector molecules. The LPS-inducible superoxide production of TNF/LT-alpha(-/-) BMDM was impaired. Accordingly both scavenging of superoxide and peroxynitrite led to reduced L. monocytogenes killing by wt BMDM. In addition, peroxynitrite was able to kill L. monocytogenes in vitro. Together these findings suggest that the defective host defense of TNF/LT-alpha-deficient mice against L. monocytogenes partially stems from reduced superoxide production of macrophages due to the absence of TNF and imply a function for peroxynitrite, the reaction product of NO and superoxide, in the intracellular killing of L. monocytogenes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; CELL-INDEPENDENT PATHWAY; NITRIC-OXIDE SYNTHASE; LISTERIA-MONOCYTOGENES; IFN-GAMMA; MURINE LISTERIOSIS; ANTIBACTERIAL RESISTANCE; INTERFERON-GAMMA; PERITONEAL-MACROPHAGES; MYCOBACTERIUM-AVIUM; macrophage; host defense; nitric oxide; superoxide; peroxynitrite |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Dec 2022 10:12 |
| Last Modified: | 20 Dec 2022 10:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48946 |
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