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: Yuichiro Kurimura, Chiaki Nishitani, Shigeru Ariki, Atsushi Saito, Yoshihiro Hasegawa, Motoko Takahashi, Jiro Hashimoto, Satoshi Takahashi, Taiji Tsukamoto, Yoshio Kuroki
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 47 Pg. 39578-88 (Nov 16 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 23012359 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adhesins, Escherichia coli
• Pulmonary Surfactant-Associated Protein D
• Tetraspanins
• UPK1A protein, human
• Upk1a protein, mouse
• Uroplakin Ia
• fimH protein, E coli
• Fimbriae Proteins

Topics

• Adhesins, Escherichia coli (genetics, metabolism)
• Animals
• Bacterial Adhesion
• Escherichia coli Infections (metabolism, pathology)
• Female
• Fimbriae Proteins (genetics, metabolism)
• Humans
• Male
• Mice
• Pulmonary Surfactant-Associated Protein D (genetics, metabolism)
• Rabbits
• Tetraspanins (biosynthesis, genetics)
• Urinary Bladder (metabolism, microbiology, pathology)
• Urinary Tract Infections (metabolism, pathology)
• Uropathogenic Escherichia coli (metabolism)
• Uroplakin Ia (biosynthesis, genetics)
• Urothelium (metabolism, microbiology, pathology)