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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 4, April, 2001 459-468

Acid Exposure Stimulates the Adherence of Streptococcus pneumoniae to Cultured Human Airway Epithelial Cells
Effects on Platelet-Activating Factor Receptor Expression

Satoshi Ishizuka, Mutsuo Yamaya, Tomoko Suzuki, Katsutoshi Nakayama, Masahito Kamanaka, Shiroh Ida, Kiyohisa Sekizawa, and Hidetada Sasaki

Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai; and Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

To examine the effects of acid exposure on the adherence of Streptococcus pneumoniae to cultured human tracheal epithelial cells, cells were exposed to acid at various pH levels, and various concentrations of S. pneumoniae were added to the culture medium. The number of S. pneumoniae adhering to cultured human tracheal epithelial cells increased after acid exposure. Y-24180, a specific inhibitor of the receptor for the platelet-activating factor (PAF) and PAF itself decreased the number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the activation of transcription factor nuclear factor (NF)-kappa B and the expression of protein and messenger RNA (mRNA) of the PAF receptor. The pyrrolidine derivative of dithiocarbamate (PDTC), an inhibitor of NF-kappa B, also decreased the number of S. pneumoniae adhering to the cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the content of interleukin (IL)-1alpha and IL-1beta in the culture supernatants, but monoclonal antibodies to IL-1alpha and IL-1beta failed to inhibit the increased number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. These findings suggest that acid exposure stimulates the adherence of S. pneumoniae to the airway epithelial cells via increases in PAF receptors. Increases in PAF receptor expression may be, in part, mediated via activation of transcription factors and subsequent PAF receptor mRNA expression by acid exposure. Increased adherence of S. pneumoniae may be one of the reasons why pneumonia develops after gastric juice aspiration.

Abbreviations: colony-forming unit, CFU; Dulbecco's modified Eagle's medium, DMEM; dithiothreitol, DTT; ethylenediaminetetraacetic acid, EDTA; enzyme-linked immunosorbent assay, ELISA; electrophoretic mobility shift assay, EMSA; fluorescein isothiocyanate, FITC; N-2-hydroxyethylpiperazine-N'-ethane sulfonic acid, Hepes; immunoglobulin, Ig; interleukin, IL; lactate dehydrogenase, LDH; messenger RNA, mRNA; nuclear factor, NF; platelet-activating factor, PAF; phosphate-buffered saline, PBS; pyrrolidine derivative of dithiocarbamate, PDTC; phenylmethylsulfonyl fluoride, PMSF; standard error of the mean, SEM; tumor necrosis factor, TNF; ultroser G serum substitute, USG.




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