title: Involvement of Escherichia coli in pathogenesis of xanthogranulomatous cholecystitis with scavenger receptor class A and CXCL16-CXCR6 interaction.
abstract: Xanthogranulomatous cholecystitis (XGC) is characterized by the infiltration of numerous foamy macrophages. Bacterial infection is thought to be involved in the pathogenesis of XGC. Using XGC and cultured murine biliary epithelial cells (BEC), the participation of E. coli and the role of the scavenger receptor class A (SCARA), as well as chemokine(C-X-C motif) ligand 16 (CXCL16) and its receptor chemokine(C-X-C motif) receptor 6 (CXCR6), were examined in the pathogenesis of XGC. E. coli components and genes were detected in XGC on immunohistochemistry and polymerase chain reaction (PCR), respectively. SCARA-recognizing E. coli was found in foamy macrophages aggregated in xanthogranulomatous lesions. CXCL16, which functions as a membrane-bound molecule and soluble chemokine to induce adhesion and migration of CXCR6(+) cells, was detected on gallbladder epithelia, and CXCR6(+)/CD8(+) T cells and CXCR6(+)/CD68(+) macrophages were also accumulated. In cultured BEC, CXCL16 mRNA and secreted soluble CXCL16 were constantly detected and upregulated by treatment with E. coli and lipopolysaccharide through Toll-like receptor 4. These suggest that SCARA in macrophages is involved in the phagocytosis of E. coli followed by foamy changes and that bacterial infection causes the upregulation of CXCL16 in gallbladder epithelia, leading to the chemoattraction of macrophages via CXCL16-CXCR6 interaction and formation of the characteristic histology of XGC.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Sawada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Kumiko
authors.initials: K
authors.lastname: Isse
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Kaizaki
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000378:metabolism*; D002764:Cholecystitis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D005260:Female; D005487:Foam Cells / Q000378:metabolism / Q000382:microbiology; D005798:Genes, Bacterial / Q000235:genetics; D006099:Granuloma / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D010587:Phagocytosis; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D015854:Up-Regulation; D014973:Xanthomatosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology