title: Apical secretion of a pathogen-elicited epithelial chemoattractant activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium.
abstract: Modeling Salmonella-epithelial cell interaction in vitro has led to the realization that epithelial cells are crucial in orchestrating neutrophil (PMN) responses, in part by stimulating basolateral release of epithelial chemokines, including IL-8. However, such basolaterally released chemokines, while likely important in orchestration of PMN movement across the subepithelial matrix, are unlikely to be responsible for the final step of transepithelial migration of PMN and entry into the apical compartment. We now show that S. typhimurium attachment to T84 cell apical epithelial membranes induces polarized apical secretion of a pathogen-elicited epithelial chemoattractant (PEEC) bioactivity. Experiments employing semipurified PEEC indicate that it is released in a polarized apical fashion and is sufficient to explain the observed final step of transepithelial migration of PMN induced by Salmonella-apical membrane interaction. By preliminary physical characterization and profiles of PMN activation, PEEC appears to be a novel PMN chemotactic bioactivity. This 1- to 3-kDa nominal molecular mass chemokine-like bioactivity directly stimulates PMN via a pertussis toxin-sensitive receptor and elicits a Ca2+ signal. While these latter features are shared by most other chemokines, analysis of PEEC-elicited PMN activation reveals that, unlike these other agonists, PEEC, even at saturating concentrations, elicits chemotactic activity in the absence of stimulation of superoxide production and/or release of primary and/or secondary granules. These data suggest that the apically released PEEC activity appears to represent a novel epithelial-derived chemoattractant that directs PMN movement across epithelial monolayers.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: McCormick
authors.forename: C A
authors.initials: CA
authors.lastname: Parkos
authors.forename: S P
authors.initials: SP
authors.lastname: Colgan
authors.forename: D K
authors.initials: DK
authors.lastname: Carnes
authors.forename: J L
authors.initials: JL
authors.lastname: Madara
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001422:Bacterial Adhesion; D015550:Cell Degranulation; D002462:Cell Membrane / Q000382:microbiology; D016764:Cell Polarity; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D009504:Neutrophils / Q000276:immunology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D018123:Receptors, Interleukin / Q000032:analysis; D023062:Receptors, Interleukin-8A; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D018000:Receptors, Peptide; C111658:pathogen-elicited epithelial chemoattractant; D013481:Superoxides