title: High levels of endogenous nitric oxide produced after burn injury in rats arrest activated T lymphocytes in the first G1 phase of the cell cycle and then induce their apoptosis.
abstract: Major physical traumas provoke a systemic inflammatory response and immune dysfunction. In a model of thermal injury in rats, we previously showed that an overproduction of nitric oxide (NO) was responsible for the collapse of lymphoproliferative responses. In the present work, we performed a time-course analysis of cell proliferation and cell death parameters in order to establish the sequence of events triggered by the high NO output in Wistar/Han rat splenocytes activated with Con A, 10 days after burn injury. We demonstrate that activated T cells from burned rats never divided whereas normal T cells underwent four division cycles. However, T cells from both burned and normal rat entered the G1 phase as shown by increase of cell size, mitochondria hyperpolarization, and expression of cyclin D1. Burned rat T cells progressed to the late G1 phase as shown by expression of the nuclear Ki-67 antigen, but they never entered the S phase. They underwent apoptosis as shown by morphological parameters, disruption of transmembrane mitochondrial potential, and DNA fragmentation. Persistent accumulation of the p53 protein accompanied these phenomena. NO synthase inhibitors antagonize alterations of cell proliferation and cell death parameters in burned rat T cells and accelerated p53 turnover.
authors.affiliation: Laboratoire de Physiologie Respiratoire, Faculté de Médecine Cochin/Port-Royal, Université Paris V, 24 rue du Faubourg Saint Jacques, 75014 Paris, France. valentilio@yahoo.fr
authors.forename: Lionel M
authors.initials: LM
authors.lastname: Valenti
authors.forename: Jacques
authors.initials: J
authors.lastname: Mathieu
authors.forename: Yves
authors.initials: Y
authors.lastname: Chancerelle
authors.forename: Martine
authors.initials: M
authors.lastname: De Sousa
authors.forename: Maryse
authors.initials: M
authors.lastname: Levacher
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Dinh-Xuan
authors.forename: Irène
authors.initials: I
authors.lastname: Florentin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002056:Burns / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D009336:Necrosis / Q000276:immunology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013843:Thiazines / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007376:Interleukin-2; D013843:Thiazines; D016159:Tumor Suppressor Protein p53; D003208:Concanavalin A; D007550:Isothiuronium; D009569:Nitric Oxide; C027744:S-methylisothiopseudouronium