FIG 6 .

Epithelial MRPs assist in controlling pro- and anti-inflammatory states. As shown by this work, lung epithelium expresses large amounts of MRP1 and small amounts of MRP2 at basal (uninfected) states. MRP1 effluxes molecules with anti-inflammatory activity, here termed L-AMEND, which acts to suppress PMN migration. During infection with Streptococcus pneumoniae, MRP1 is reduced and MRP2 increases on the apical surface of the epithelium. MRP2 mediates release of the proinflammatory molecule hepoxilin A3 (HXA₃), which creates a chemokine gradient to draw PMNs to the site of infection. By both reducing MRP1 and increasing MRP2, the epithelium works to maximize the transepithelial PMN migration; however, this PMN migration also disrupts epithelial tight junctions and can lead to infiltration of the intruding S. pneumoniae.