Leukotriene A₄-hydrolase expression and leukotriene B₄ levels in chronic inflammation of bacterial origin

Abstract.

Chronic inflammation of the oral epithelium of bacterial origin is associated with elevated leukotriene B₄ (LTB₄) levels. We investigated leukotriene A₄ (LTA₄)-hydrolase expression and LTB₄ levels in oral epithelium in relation to the clinical disease manifestation and immunohistopathology and LTA₄-hydrolase expression in cultured oral keratinocytes. In 11 patients, three different types of biopsy specimens of the oral mucosa tissues were examined . Each sample was divided, and one-half was analysed using immunohistochemistry with antibodies to LTA₄-hydrolase, CD1a, CD3, CD19, macrophages/monocytes and granulocytes. The other half of the sample was homogenised and analysed using reverse-phase high-performance liquid chromatography to determine LTB₄ levels. We found strong LTA₄-hydrolase expression in basal cells of the oral epithelium from tissue samples that appeared clinically healthy; however, histologically a mild chronic inflammation was observed. In contrast, patients with symptoms of an inflammation of the oral mucosa showed only weak LTA₄-hydrolase staining of the epithelial cell layers, but strong immunoreactivity in endothelial and invading inflammatory cells. LTB₄ levels were elevated in inflamed tissues compared with non-inflamed controls. Most significantly, there was a strong association between the immunohistochemical detection of the enzyme, LTB₄ levels, cellular infiltration and the clinical disease manifestations. In vitro experiments indicated that LTA₄-hydrolase expression may be induced by bacterial contamination. This study suggests that LTA₄-hydrolase expression and elevated LTB₄ levels in oral mucosal epithelium are integral parts of the induction and progression of chronic inflammatory reactions. Epithelial cells may participate in early stages of inflammation as a source of LTB₄.