Pneumococcus activation of the 5-lipoxygenase pathway and production of glycoproteins in the middle ear of rats

Pneumococcal otitis media is associated with the production of potent in¯ammatory me-diators (leukotrienes), but the mechanism by which pneumococcus induces production of leukotrienes in the middle ear is poorly understood. In this study, up-regulation of 2 genes that govern the lipoxygenase pathway, cPLA2 and 5-LOX, was observed in rats following inoculation of pneumococcus into the middle ear cavity. Expression of cPLA2 was low, and 5-LOX gene expression was not detected in control animals. Up-regulation of cPLA2 and 5-LOX in middle ear epithelial cells was accompanied by an increase of high-molecular-weight glycoproteins in middle ear ¯uid and cells. These ®ndings suggest that pneumococcus activates the lipoxygenase pathway by up-regulating expression of the cPLA2 and 5-LOX genes. This, in turn, may stimulate synthesis and secretion of high-molecular-weight glycoproteins that facilitate production of ¯uid in the middle ear cleft. Streptococcus pneumoniae is the most common middle ear pathogen in childhood acute otitis media (OM). Nearly every child in the United States experiences an ear infection by the age of 5 years. Studies indicate that infection of the middle ea