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Nitric oxide inhibits spleen cell proliferative response after burn injury by inducing cytostasis, apoptosis, and necrosis of activated T lymphocytes: role of the guanylate cyclase
- Source :
- Cellular Immunology. 221:50-63
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- We previously showed that an overproduction of nitric oxide (NO) by macrophages was responsible for the collapse of lymphoproliferative responses after burn injury in rats. First, we demonstrate here that 10 days post-burn, the inhibition of splenocyte response to concanavalin-A results from cytostatic, apoptotic, and necrotic effects of NO on activated T cells. This was evidenced by various criteria at the levels of DNA, mitochondria, and plasma membrane. Inhibition of NO synthase by S-methylisothiourea (10 microM) normalized all the parameters. Second, we show that two soluble guanylate cyclase (sGC) inhibitors, LY83583 and ODQ, restored the proliferative response in a concentration-dependent manner. LY83583 (0.5 microM) rescued T cells from apoptosis. Similar results were obtained with KT5823 (5 microM) a specific inhibitor of protein kinase G (PKG). In contrast, neither LY83583 nor KT5823 inhibited NO-induced necrosis. These results suggest that NO blocked T cells in the G1 phase and induced apoptosis through a sGC-PKG-dependent pathway and necrosis through an independent one.
- Subjects :
- Male
GUCY1B3
medicine.medical_specialty
Indoles
Necrosis
T-Lymphocytes
Immunology
Carbazoles
Apoptosis
Biology
Lymphocyte Activation
Nitric Oxide
Nitric oxide
chemistry.chemical_compound
Alkaloids
Quinoxalines
Internal medicine
Splenocyte
medicine
Animals
Enzyme Inhibitors
Rats, Wistar
Protein Kinase Inhibitors
Cells, Cultured
Skin
Oxadiazoles
GUCY1A3
Guanylate cyclase 2C
Cytostasis
Molecular biology
Rats
Endocrinology
chemistry
Guanylate Cyclase
Aminoquinolines
medicine.symptom
Burns
Cell Division
Spleen
Subjects
Details
- ISSN :
- 00088749
- Volume :
- 221
- Database :
- OpenAIRE
- Journal :
- Cellular Immunology
- Accession number :
- edsair.doi.dedup.....12eee66a7054c1ac1d6261bd75d5b7bf