Role of lipopolysaccharide in signaling to subepithelial polymorphonuclear leukocytes.
Polymorphonuclear leukocyte (PMN) infiltration and migration across colonic intestinal epithelia is a hallmark of inflammation in Shigella flexneri-mediated dysentery. To identify bacterial signals associated with this process, potential stimulatory factors mediating initial PMN association with the epithelium and subsequent transepithelial migration were examined in an in vitro model system. Quantitative analyses revealed that purified S. flexneri lipopolysaccharide (LPS) deposited at the apical surface of polarized intestinal epithelial cells transcytosed to the basolateral pole, a process dependent on the stage of epithelial 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 enhanced PMN adherence. In addition, LPS stimulated a significant degree of directed transepithelial migration of PMNs, an event that was further enhanced in the presence of NHS. These results implicate LPS in signaling subepithelial PMN emigration and enhancing PMN-epithelium interactions prior to and during subsequent Shigella-induced transepithelial migration.
Beatty
W L
WL
Unité de Pathogénie Microbienne Moléculaire, U389, Institut Nationale de la Santé et de la Recherche Médicale, Institut Pasteur, Paris, France.
Sansonetti
P J
PJ
D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003106:Colon / Q000166:cytology; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D012763:Shigella flexneri / Q000472:pathogenicity*
D016209:Interleukin-8; D008070:Lipopolysaccharides