NDLI: Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

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Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

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Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bimczok, Diane Smith, Phillip D. Smythies, Lesley E. Mannon, Peter J. Wilcox, C. Mel Stahl, Richard D. Das, Soumita Peter, Shajan Grams, Jayleen M. Waites, Ken B. Ernst, Peter B. Harris, Paul R.
Description	Country affiliation: United States Author Affiliation: Bimczok D ( Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.)
Abstract	Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF- , which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1203330
Journal	The Journal of Immunology
Issue Number	12
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apoptosis Physiology Epithelial Cells Pathology Helicobacter Infections Immunology Leukocytes, Mononuclear Macrophages Flow Cytometry Fluorescent Antibody Technique Gastric Mucosa Cytology Helicobacter Pylori In Situ Nick-end Labeling Phagocytosis Reverse Transcriptase Polymerase Chain Reaction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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