Nitric oxide as a regulatory and effector molecule in the immune system
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12009578
DOI
10.1016/s0161-5890(02)00027-5
PII: S0161589002000275
Knihovny.cz E-resources
- MeSH
- Cytokines biosynthesis MeSH
- Enzyme Inhibitors pharmacology MeSH
- Kinetics MeSH
- Cells, Cultured MeSH
- Macrophages immunology MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Nitric Oxide physiology MeSH
- Graft Survival drug effects immunology MeSH
- Graft Rejection immunology MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase antagonists & inhibitors MeSH
- T-Lymphocyte Subsets drug effects immunology MeSH
- Thiazines pharmacology MeSH
- Skin Transplantation immunology MeSH
- Transplantation Tolerance MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine MeSH Browser
- Cytokines MeSH
- Enzyme Inhibitors MeSH
- Nos2 protein, mouse MeSH Browser
- Nitric Oxide MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase MeSH
- Thiazines MeSH
Nitric oxide (NO) as a small ubiquitous molecule influencing a great variety of biological processes in the organism. Within the immune system, increased levels of NO were observed in various immunopathological situations, inflammatory reactions and during the response to transplantation and tumour antigens. It appears that NO can influence various facets of immune response. We studied involvement and the role of NO in immune response to skin allograft in mice. The production of NO at the site of graft rejection correlated well with the kinetic of rejection reaction and with the fate of the allograft. Graft infiltrating macrophages were identified as a principal cell population producing NO and the production of NO by macrophages was dependent on the presence of activated CD4(+) T cells. Survival of skin allografts was significantly prolonged by the treatment of graft recipients with 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a specific inhibitor of inducible NO synthase (iNOS). These results suggest a role for NO as the effector cytotoxic molecule involved in the graft rejection. Experiments in vitro demonstrated that NO, in addition to its effector function, acts as a modulator of cytokine production. Spleen cells stimulated with alloantigens in the presence of AMT or S-ethylisothiourea (EIT), an another selective iNOS inhibitor, produced considerably more interleukin (IL)-4 and IL-10 than the cells stimulated in the absence of iNOS inhibitors. The production of Th1 cytokines IL-2 and interferon (IFN)-gamma was not enhanced by the inhibition of NO synthesis. The results altogether show that NO can act in transplantation reactions as an immunomodulator on cytokine production level and as an effector molecule involved in the graft destruction.
References provided by Crossref.org
