Apoptotic extracellular vesicle formation via local phosphatidylserine exposure drives efficient cell extrusion.

Cell extrusion is a universal mode of cell removal from tissues, and it plays an important role in regulating cell numbers and eliminating unwanted cells. However, the underlying mechanisms of cell delamination from the cell layer are unclear. Here, we report a conserved execution mechanism of apoptotic cell extrusion. We found extracellular vesicle (EV) formation in extruding mammalian and Drosophila cells at a site opposite to the extrusion direction. Lipid-scramblase-mediated local exposure of phosphatidylserine is responsible for EV formation and is crucial for executing cell extrusion. Inhibition of this process disrupts prompt cell delamination and tissue homeostasis. Although the EV has hallmarks of an apoptotic body, its formation is governed by the mechanism of microvesicle formation. Experimental and mathematical modeling analysis illustrated that EV formation promotes neighboring cells' invasion. This study showed that membrane dynamics play a crucial role in cell exit by connecting the actions of the extruding cell and neighboring cells.

[A case of serious aspiration pneumonia associated with multiple cerebral infarctions and Alzheimer's disease followed by hospital and home care service team].

A 81-year-old man, who had been diagnosed in multiple cerebral infarction and Alzheimer's disease, was followed up in his local clinic since 1997. He had been bedridden before admission, but could eat. He was admitted with severe aspiration pneumonia in December 1999. Since severe dementia and dysphagia were noted after admission, he was examined to find out whether or not he could swallow while the treatment of his pneumonia was conducted at the same time. The water swallowing test indicated a risk of aspiration, thus, percutaneous endoscopic gastrostomy was performed on January 26, 2000 after the completion of the treatment for pneumonia. Although the patient's condition was complicated by aspiration pneumonia, enteral feeding through the gastric fistula gradually became successful, and he was discharged in June 2000. His family physician followed him up by visiting at home to examine and observe his general physical condition including consciousness, vital signs, skin and respiration, while taking measures in cooperation with the local health care visiting nurse. The patient, thereafter, was repeatedly admitted and discharged because of exacerbation and remission of symptoms, including coughing, sputum and fever, probably caused by aspiration pneumonia. When he was admitted in December 2001, which was his sixth admission, since there were troubles with the infusion tube and frequent gastroesophageal reflux, the gastric fistula management was judged to be a great burden on the patient. In January 2002, the gastrostomy tube was removed and the patients, whose alimentation was managed using intra-venous hyperalimentation (IVH), was discharged. Besides periodic visits by his family physician, a 24-hour house visit system was introduced to control his IVH and deal with his family members' anxiety. His general condition, thereafter, has not markedly changed. The patient has continuously received medical treatment for 14 months after being discharged and his condition is stable.