ROLE OF LIPOPOLYSACCHARIDE IN SIGNALING TO SUBEPITHELIAL POLYMORPHONUCLEAR LEUKOCYTES

Polymorphonuclear leukocyte (PMN) infiltration and migration across co lonic intestinal epithelia is a hallmark of inflammation in Shigella f lexneri-mediated dysentery. To identify bacterial signals associated w ith this process, potential stimulatory factors mediating initial PMN association,vith the epithelium and subsequent transepithelial migrati on were examined in an in vitro model system. Quantitative analyses re vealed that purified S. flexneri lipopolysaccharide (LPS) deposited at the apical surface of polarized intestinal epithelial cells transcyto sed to the basolateral pole, a process dependent on the stage of epith elial cell differentiation. Transcytosed LPS in the presence of normal human serum (NHS), a source of LPS binding protein and soluble CD14, mediated both interleukin-8 secretion at the basolateral pole and enha nced PMN adherence. In addition, LPS stimulated a significant degree o f directed transepithelial migration of PMNs, an event that was furthe r enhanced in the presence of MHS. These results implicate LPS in sign aling subepithelial PMN emigration and enhancing PMN-epithelium intera ctions prior to and during subsequent Shigella-induced transepithelial migration.