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Supported by grants (GM44118 and GM55194) from the National Institutes of Health and by the Leukemia and Lymphoma Society of America, the National Health and Medical Research Council of Australia, and the Alan A. Wolff Foundation. Hotchkiss reports receiving grant support from Pfizer, and Dr. Strasser, consulting fees from Genentech and Abbott Laboratories and grant support from Genentech. No other potential conflict of interest relevant to this article was reported.
Eizo Watanabe for providing electron-microscopical images of liver samples; Dr. Helen Liapis for providing electron-microscopical images of kidney samples; Dr. Kevin Tinsley for performing immunohistochemical staining of many tissue sections; Drs.
Craig Coopersmith, Timothy Buchman, and J. Perren Cobb for many stimulating discussions and assisting in tissue sampling; and many other cell-death investigators for their work and inspiration. Source Information From the Departments of Anesthesiology (R.S.H., J.E.M.), Medicine (R.S.H.), and Surgery (R.S.H.), Washington University School of Medicine, St. Louis; the Department of Molecular Genetics of Cancer, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia (A.S.); and the Department of Pathology, University of Washington School of Medicine, Seattle (P.E.S.). Address reprint requests to Dr. Hotchkiss at the Department of Anesthesiology, Washington University School of Medicine, 660 S.
Louis, MO 63110,. Figure 2 Apoptotic Cells in Thymus, Liver, and Intestine. Panel A is an electron-microscopical image of a phagocytic cell that has engulfed multiple apoptotic thymocytes. The compacted thymocyte nuclei have a classic crescent-shaped appearance, owing to layering of chromatin along the nuclear membrane (arrows). Normal-appearing nuclei are present at the top and bottom of the field of view (uranyl acetate–lead citrate).
The thymic tissue section was obtained from a 26-year-old woman who died after a motor vehicle accident and whose condition was complicated by the acute respiratory distress syndrome and sepsis. Panel B shows a single apoptotic hepatocyte (arrow) containing multiple compacted nuclear fragments indicative of apoptosis (hematoxylin and eosin). The sample was obtained from an 81-year-old man who had been injured in a motor vehicle accident and whose condition was complicated by ventilator-associated pneumonia. Panel C shows two adjacent crypts in colonic mucosa that had immunohistochemical staining for cytokeratin 18 cleavage fragments (brown).
Cytokeratin 18 is cleaved by active caspases in both intrinsic and extrinsic apoptotic pathways. Detached cells in crypt lumens and epithelial cells that are still integrated into the crypt lining are positive; these cells also have classic apoptotic nuclear morphology (cytokeratin 18 immunostaining [clone M30] and diaminobenzidine with hematoxylin counterstaining). The tissue sample was obtained from a 24-year-old man who had aortic dissection and bowel ischemia after a motor vehicle accident. Panel D shows colonic intestinal epithelial cells with characteristic apoptotic features of nuclear compaction and fragmentation; the epithelial cells have been sloughed into the bowel lumen (hematoxylin and eosin). The sample was obtained from a 23-year-old patient with ischemic injury to the bowel after intestinal surgery.