Learn More
BACKGROUND 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. METHODS AND RESULTS Using 5(More)
OBJECTIVE T cell-induced cytotoxicity, of which granzyme B is a key mediator, is believed to contribute to the pathogenesis of inflammatory vascular diseases. In this report, we investigate the mechanism of granzyme B-induced smooth muscle cell (SMC) death. METHODS AND RESULTS The addition of purified granzyme B alone to cultured SMCs caused a significant(More)
Treatment with the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) followed by irradiation with visible light induces apoptosis in human acute myelogenous leukaemia HL-60 cells. Photoactivation of BPD-MA induces procaspase 3 (CPP32/Yama/apopain) and procaspase 6 (Mch2) cleavage into their proteolytically active subunits in(More)
Ischemia and reperfusion both contribute to tissue damage after myocardial infarction. Although many drugs have been shown to reduce infarct size when administered before ischemia, few have been shown to be effective when administered at reperfusion. Moreover, although it is generally accepted that a burst of reactive oxygen species (ROS) occurs at the(More)
Interferon-α (IFN-α) is essential for antiviral immunity, but in the absence of matrix metalloproteinase-12 (MMP-12) or IκBα (encoded by NFKBIA) we show that IFN-α is retained in the cytosol of virus-infected cells and is not secreted. Our findings suggest that activated IκBα mediates the export of IFN-α from virus-infected cells and that the inability of(More)
Numerous murine models are available for the study of the human aging process. Most of these models are based on known mutations that cause progeroid disease in humans or are involved in DNA repair and cell senescence. While these models certainly have contributed to our knowledge of age-related diseases, none adequately represent the range of human(More)
OBJECTIVE Granzyme B (GrB) is a pro-apoptotic serine protease that contributes to immune-mediated target cell apoptosis. However, during inflammation, GrB accumulates in the extracellular space, retains its activity, and is capable of cleaving extracellular matrix (ECM) proteins. Recent studies have implicated a pathogenic extracellular role for GrB in(More)
We report that the photosensitizer verteporfin kills lymphoma cells by an apoptotic process involving a dissipation of the mitochondrial inner transmembrane potential (deltapsim). Light-activated verteporfin-induced apoptosis was abolished by transfection with Bcl-2, a procedure reported to inhibit the mitochondrial permeability transition pore complex(More)
Apolipoprotein E knockout (apoE-KO) mice have been utilized for decades as a model of atherosclerosis. However, in addition to atherosclerosis, apoE-KO mice develop extensive cutaneous xanthomatosis, accelerated skin aging and frailty when fed a high fat diet. Granzyme B (GrB) is a pro-apoptotic serine protease that has recently been shown to exhibit(More)
Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechanism involving ECM cleavage. The murine(More)