title: 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.
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.
authors: 2Division of Comparative Pathology and Medicine, Department of Pathology, MC 0063, University of California, San Diego, San Diego, CA 92093-0063, USA. pernst@ucsd.edu.
authors: Soumita
authors: S
authors: Das
authors: Arup
authors: A
authors: Sarkar
authors: Kieran A
authors: KA
authors: Ryan
authors: Sarah
authors: S
authors: Fox
authors: Alice H
authors: AH
authors: Berger
authors: Ignacio J
authors: IJ
authors: Juncadella
authors: Diane
authors: D
authors: Bimczok
authors: Lesley E
authors: LE
authors: Smythies
authors: Paul R
authors: PR
authors: Harris
authors: Kodi S
authors: KS
authors: Ravichandran
authors: Sheila E
authors: SE
authors: Crowe
authors: Phillip D
authors: PD
authors: Smith
authors: Peter B
authors: PB
authors: Ernst
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D017209:Apoptosis; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology; D005756:Gastritis / Q000378:metabolism; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled; D013270:Stomach / Q000166:cytology / Q000382:microbiology
chemical_list: C468226:ADGRB1 protein, human; D042501:Angiogenic Proteins; D016207:Cytokines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C408123:phosphatidylserine receptor
keywords: bacteria; efferocytosis; gastritis; mucosal immunity; stomach