Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis
It has been reported that levels of neopterin are elevated in the cerebrospinal fluid (CSF) of patients with bacterial meningitis, and that neopterin enhances cell death induced by H2O2 in mouse monocytes and macrophages. In the present study, we examined the relationship between the disappearance o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2011-02-01
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| Series: | Pteridines |
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| Online Access: | https://doi.org/10.1515/pteridines.2011.22.1.91 |
| _version_ | 1818732833767686144 |
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| author | Kawakami Yasuhiko Tsukimoto Mitsutoshi Kuwabara Kentaro Fujita Takehisa Fujino Osamu Kojima Shuji Fukunaga Yoshitaka |
| author_facet | Kawakami Yasuhiko Tsukimoto Mitsutoshi Kuwabara Kentaro Fujita Takehisa Fujino Osamu Kojima Shuji Fukunaga Yoshitaka |
| author_sort | Kawakami Yasuhiko |
| collection | DOAJ |
| description | It has been reported that levels of neopterin are elevated in the cerebrospinal fluid (CSF) of patients with bacterial meningitis, and that neopterin enhances cell death induced by H2O2 in mouse monocytes and macrophages. In the present study, we examined the relationship between the disappearance of inflammatory cells in the CSF of patients with bacterial meningitis and the effects of neopterin on cell death. We hypothesized that the rapid cell death of mononuclear leukocytes (MNs) and survival of polymorphonuclear leukocytes (PMNs) brought about by high levels of tumor necrosis factor-a TNF-a may be related to the pathophysiology of PMN predominance in the CSF of patients with bacterial meningitis. Peripheral blood leukocytes separated into two fractions (MNs and PMNs) were suspended in CSF samples from patients with bacterial meningitis, and the cell death rate was determined with MTT assay. The higher the CSF TNF-a level, the higher the MN mortality rate tended to be. In contrast, PMNs were able to survive high levels of TNF-a in the CSF. For control purposes, MNs and PMNs were also suspended in various conditioned media. The same association between TNF-a levels and MN mortality was observed, as was the survival of PMNs. The addition of neopterin enhanced the cytocidal effect of TNF. The present study suggests that neopterin is related to PMN predominance in the CSF of patients with bacterial meningitis via the effect of TNF-a on cell death. |
| first_indexed | 2024-12-17T23:39:51Z |
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| institution | Directory Open Access Journal |
| issn | 0933-4807 2195-4720 |
| language | English |
| last_indexed | 2024-12-17T23:39:51Z |
| publishDate | 2011-02-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Pteridines |
| spelling | doaj.art-ded030bb7b7240bf86b42943cb1f27b92022-12-21T21:28:28ZengDe GruyterPteridines0933-48072195-47202011-02-01221919610.1515/pteridines.2011.22.1.91Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial MeningitisKawakami Yasuhiko0Tsukimoto Mitsutoshi1Kuwabara Kentaro2Fujita Takehisa3Fujino Osamu4Kojima Shuji5Fukunaga Yoshitaka6Department of Pediatrics, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama-city, Tokyo 216-8512, Japan, Tel.: +81-42-371-2111; fax: +81-42-372- 7377Department of Radiation Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, JapanDepartment of Pediatrics, Nippon Medical School, JapanDepartment of Pediatrics, Nippon Medical School, JapanDepartment of Pediatrics, Nippon Medical School, JapanDepartment of Radiation Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, JapanDepartment of Pediatrics, Nippon Medical School, JapanIt has been reported that levels of neopterin are elevated in the cerebrospinal fluid (CSF) of patients with bacterial meningitis, and that neopterin enhances cell death induced by H2O2 in mouse monocytes and macrophages. In the present study, we examined the relationship between the disappearance of inflammatory cells in the CSF of patients with bacterial meningitis and the effects of neopterin on cell death. We hypothesized that the rapid cell death of mononuclear leukocytes (MNs) and survival of polymorphonuclear leukocytes (PMNs) brought about by high levels of tumor necrosis factor-a TNF-a may be related to the pathophysiology of PMN predominance in the CSF of patients with bacterial meningitis. Peripheral blood leukocytes separated into two fractions (MNs and PMNs) were suspended in CSF samples from patients with bacterial meningitis, and the cell death rate was determined with MTT assay. The higher the CSF TNF-a level, the higher the MN mortality rate tended to be. In contrast, PMNs were able to survive high levels of TNF-a in the CSF. For control purposes, MNs and PMNs were also suspended in various conditioned media. The same association between TNF-a levels and MN mortality was observed, as was the survival of PMNs. The addition of neopterin enhanced the cytocidal effect of TNF. The present study suggests that neopterin is related to PMN predominance in the CSF of patients with bacterial meningitis via the effect of TNF-a on cell death.https://doi.org/10.1515/pteridines.2011.22.1.91neopterintumor necrosis factor-alphabacterial meningitispolymorphonuclear leukocytesmononuclear leukocytescerebrospinal fluidcell death |
| spellingShingle | Kawakami Yasuhiko Tsukimoto Mitsutoshi Kuwabara Kentaro Fujita Takehisa Fujino Osamu Kojima Shuji Fukunaga Yoshitaka Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis Pteridines neopterin tumor necrosis factor-alpha bacterial meningitis polymorphonuclear leukocytes mononuclear leukocytes cerebrospinal fluid cell death |
| title | Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis |
| title_full | Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis |
| title_fullStr | Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis |
| title_full_unstemmed | Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis |
| title_short | Neopterin May Enhance TNF-a-mediated Mononuclear Cell Death in the Cerebrospinal Fluid of Patients with Bacterial Meningitis |
| title_sort | neopterin may enhance tnf a mediated mononuclear cell death in the cerebrospinal fluid of patients with bacterial meningitis |
| topic | neopterin tumor necrosis factor-alpha bacterial meningitis polymorphonuclear leukocytes mononuclear leukocytes cerebrospinal fluid cell death |
| url | https://doi.org/10.1515/pteridines.2011.22.1.91 |
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