Attenuated acute cardiac rejection in NOS2 -/- recipients correlates with reduced apoptosis

The mechanisms through which NOS2-mediated pathways regulate graft failure in acute cardiac rejection are ill defined. To determine whether apoptosis promoted by NOS2 may contribute, we used a heterotopic transplant model to study mouse cardiac allografts placed in recipients with targeted gene dele...

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Veröffentlicht in:	Circulation (New York, N.Y.) N.Y.), 1999-02, Vol.99 (6), p.836-842
Hauptverfasser:	KOGLIN, J, GRANVILLE, D. J, GLYSING-JENSEN, T, MUDGETT, J. S, CARTHY, C. M, MCMANUS, B. M, RUSSELL, M. E
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Apoptosis - immunology Biological and medical sciences Caspase 3 Caspases - metabolism Coumarins - pharmacology Cysteine Proteinase Inhibitors - pharmacology DNA Primers Enzyme Activation - drug effects Gene Expression Regulation, Enzymologic Graft Rejection - enzymology Heart Transplantation In Situ Nick-End Labeling Medical sciences Mice Mice, Inbred CBA Mice, Knockout Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - enzymology Muscle Fibers, Skeletal - transplantation Myocardium - chemistry Myocardium - cytology Myocardium - enzymology Nitrates - analysis Nitric Oxide Synthase - genetics Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Oligopeptides - pharmacology Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Proteins - metabolism RNA, Messenger - analysis Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Transplantation Immunology Transplantation, Homologous Tumor Suppressor Protein p53 - genetics Tyrosine - analysis
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Zusammenfassung:	The mechanisms through which NOS2-mediated pathways regulate graft failure in acute cardiac rejection are ill defined. To determine whether apoptosis promoted by NOS2 may contribute, we used a heterotopic transplant model to study mouse cardiac allografts placed in recipients with targeted gene deletion of NOS2. Using 5 different indexes of apoptosis, we showed that mouse cardiac allografts placed in NOS2 -/- recipients (n=7) had reduced apoptotic activity compared with those in NOS2 +/+ controls (n=8). There were significantly fewer TUNEL-positive nuclei per high-powered field (P
ISSN:	0009-7322 1524-4539
DOI:	10.1161/01.CIR.99.6.836