Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells
Year: 2014
Type: article
Abstract: ABSTRACT After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5‐fold increase in the binding of apoptotic GECs to THP‐1 cells or peripheral blood monocyte‐derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP‐1 cells to apoptotic cells inhibited IL‐6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti‐inflammatory effects.—Das, S., Sarkar, A., Ryan, K. A., Fox, S., Berger, A. H., Juncadella, I. J., Bimczok, D., Smythies, L. E., Harris, P. R., Ravichandran, K. S., Crowe, S. E., Smith, P. D., Ernst, P. B. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells. FASEB J . 28, 2214–2224 (2014). www.fasebj.org
Source: The FASEB Journal
DOI: 10.1096/fj.13-243238
Institutions: University of California San Diego, University College Cork, APC Microbiome Institute, Broad Institute, Harvard University, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, University of Virginia, University of Alabama at Birmingham, UAB Medicine, Pontificia Universidad Católica de Chile
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Institutes of Health, Digestive Diseases Research Core Center, University of Chicago, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: G1151965871, G1268904433, G1624440437, G1747132829, G1932852748, G207772888, EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT, The Role of the Adenosine Receptor in Th Cell Development and Function, G3046329283, G3468549464, Mucosal HIV and Immunobiology Center, G4295299954, G4536814575, G4602386074, G4719761536, G499753431, G5271353037, G5608525850, University of California San Diego Neuroscience Microscopy Imaging Core, G6323196245, G6835207951, G705904519, G712306552, G7318946674, Specialized Cancer Center Support Grant, G83478885, G8898014691, G9000007259, G9000142879, G9000152487, G9000213358, G9000215649, G9000224261, G9000326761, G912552041
OpenAlex ID: W2127157806