Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characterized by the collapse and disappearance of cell membranes and nuclear envelopes. It is well known that production of reactive oxygen species (ROS) triggers NETosis and NET formation. However, details of intracellular signaling downstream of ROS production during NETosis and NET formation remains uncertain. Here, we demonstrated that the peroxidation of phospholipids plays a critical role in NETosis and NET formation induced by phorbol 12-myristate13-acetate (PMA) or immune complex in vitro and by lipopolysaccharide (LPS) in vivo. This phospholipid peroxidation is mediated by the enzymatic activity of MPO. On the other hand, NE, which was previously reported to be released from granules to cytosol by MPO during NET formation, is not required for either the peroxidation of phospholipids or the execution of NETosis, but contributes to chromatin decondensation and nuclear swelling independently of MPO-mediated oxidized phospholipids. Analysis of isolated nuclei clearly demonstrated that oxidized phospholipids and NE differently yet synergistically execute chromatin decondensation and nuclear swelling, and the subsequent release of nuclear contents. These findings indicate the dual roles of MPO in NETosis and NET formation, and provide new insight into the molecular mechanism of these phenomena.
Pure magnesium and its alloys are biocompatible and biodegradable. In cardiovascular surgery, they have been experimentally applied for short-term use as tiny devices. Many studies have been performed on rats and mice using X-ray imaging and CT scanning. However, these small animals have a low radiation resistance and the lethal exposure dosage is small. In orthopedic surgery, fracture xation using magnesium materials has high potential applicability. Although long-term stable xation is required, few long-term animal studies have been performed. Therefore, many unclear issues still remain. Accordingly a long-term animal study was performed on Dutch rabbits to investigate the biodegradation of pure magnesium. Specimens implanted into rabbit femurs showed a volume reduction of 40-50% at 52 weeks. Bone resorption was observed in cancellous bone, and new bone formation and direct contact were partially observed. No magnesium hydroxide was observed in the surrounding area.
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