title: Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract.
abstract: The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a lectin located at bacterial pili, and their interaction initiates UPEC infection. Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in various tissues besides the lung. However, the functions of SP-D in the non-pulmonary tissues are poorly understood. The purposes of this study were to investigate the possible function of SP-D expressed in the bladder urothelium and the mechanisms by which SP-D functions. SP-D was expressed in human bladder mucosa, and its mRNA was increased in the bladder of the UPEC infection model in mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca(2+)-dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial adherence to 5637 cells, the human bladder cell line, and the UPEC-induced cytotoxicity. In addition, preincubation of SP-D with 5637 cells resulted in the decreased adherence of UPEC to the cells and in a reduced number of cells injured by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding. Consistent with the in vitro data, the exogenous administration of SP-D inhibited UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice. These results support the conclusion that SP-D can protect the bladder urothelium against UPEC infection and suggest a possible function of SP-D in urinary tract.
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kurimura
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nishitani
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ariki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Jiro
authors.initials: J
authors.lastname: Hashimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
mesh_terms: D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000473:pathology; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D059470:Tetraspanins / Q000096:biosynthesis / Q000235:genetics; D001743:Urinary Bladder / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000378:metabolism*; D060167:Uroplakin Ia / Q000096:biosynthesis / Q000235:genetics; D019459:Urothelium / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D018830:Adhesins, Escherichia coli; D037663:Pulmonary Surfactant-Associated Protein D; D059470:Tetraspanins; C086451:UPK1A protein, human; C490123:Upk1a protein, mouse; D060167:Uroplakin Ia; C058769:fimH protein, E coli; D036781:Fimbriae Proteins