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Cells 2012, 1(2), 74-88; doi:10.3390/cells1020074

Immunohistochemistry of Programmed Cell Death in Archival Human Pathology Specimens

1
Division of Immunology, Department of Infection and Immunity, Institute Research Center (Health Research Course), Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan
2
Department of Pathology, China Medical University, 92 Bei Er Ma Lu, He Ping Qu, Shenyang 110001, China
3
Department of Pathology, Graduate School of Medicine, Faculty of Medicine, Osaka University, Yamadaoka 565-0871, Suita, Japan
4
Chronic Viral Diseases Division of Molecular Pathology, Center for Chronic Viral Diseases (Infection and Immunity), Institute Research Center (Health Research Course), Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan
5
Division of Pediatrics, Department of Developmental Medicine, Institute Research Center (Heath Research Course), Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan
6
Division of Dermatology, Department of Sensory Organology, Institute Research Center (Advanced Therapeutics Course), Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan
7
Chronic Viral Diseases Division of Persistent & Oncogenic Viruses, Center for Chronic Viral Diseases (Infection and Immunity), Institute Research Center (Health Research Course), Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan
Present address: INAMORI Frontier Research Center, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
*
Author to whom correspondence should be addressed.
Received: 24 March 2012 / Revised: 5 April 2012 / Accepted: 28 April 2012 / Published: 7 May 2012
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Abstract

Immunohistochemistry (IHC) for detecting key signal molecules involved in programmed cell death (PCD) in archival human pathology specimens is fairly well established. Detection of cleaved caspase-3 in lymphocytes in rheumatoid arthritis (RA) and gastric surface foveolar glandular epithelia but not in synoviocytes in RA, gastric fundic glandular epithelia, or nasal NK/T-cell lymphoma (NKTCL) cells suggests anti-apoptotic mechanisms in cell differentiation and in oncogenesis such as the induction of survivin. Enzymatically pretreated and ultra-super sensitive detection of beclin-1 in synoviocytes in RA and gastric fundic glandular epithelia suggests enhanced autophagy. The deposition of beclin-1 in fibrinoid necrosis in RA and expression of beclin-1 in detached gastric fundic glandular cells suggest that enhanced autophagy undergoes autophagic cell death (ACD). NKTCL exhibited enhanced autophagy through LC3 labeling and showed densely LC3 labeled cell-debris in regions of peculiar necrosis without deposition of beclin-1, indicating massive ACD in NKTCL and the alternative pathway enhancing autophagy following autophagic vesicle nucleation. Autophagy progression was monitored by labeling aggregated mitochondria and cathepsin D. The cell-debris in massive ACD in NKTCL were positive for 8-hydroxydeoxyguanosine, suggesting DNA oxidation occurred in ACD. Immunohistochemical autophagy and PCD analysis in archival human pathology specimens may offer new insights into autophagy in humans. View Full-Text
Keywords: antigen retrieval and immunohistochemistry; programmed cell death; apoptosis; autophagy; archival formalin-fixed and paraffin-embedded human pathology specimen antigen retrieval and immunohistochemistry; programmed cell death; apoptosis; autophagy; archival formalin-fixed and paraffin-embedded human pathology specimen
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MDPI and ACS Style

Hasui, K.; Nagai, T.; Wang, J.; Jia, X.; Aozasa, K.; Izumo, S.; Kawano, Y.; Kanekura, T.; Eizuru, Y.; Matsuyama, T. Immunohistochemistry of Programmed Cell Death in Archival Human Pathology Specimens. Cells 2012, 1, 74-88.

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