Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
hPepT1-mediated epithelial transport of bacteria-derived chemotactic peptides enhances neutrophil-epithelial interactions.
Merlin D
,
Steel A
,
Gewirtz AT
,
Si-Tahar M
,
Hediger MA
,
Madara JL
.
???displayArticle.abstract???
Intestinal epithelial cells express hPepT1, an apical transporter responsible for the uptake of a broad array of small peptides. As these could conceivably include n-formyl peptides, we examined whether hPepT1 could transport the model n-formylated peptide fMLP and, if so, whether such cellular uptake of fMLP influenced neutrophil-epithelial interactions. fMLP uptake into oocytes was enhanced by hPepT1 expression. In addition, fMLP competitively inhibited uptake of a known hPepT1 substrate (glycylsarcosine) in hPepT1 expressing oocytes. hPepT1 peptide uptake was further examined in a polarized human intestinal epithelial cell line (Caco2-BBE) known to express this transporter. Epithelial monolayers internalized apical fMLP in a fashion that was competitively inhibited by other hPepT1 recognized solutes, but not by related solutes that were not transported by hPepT1. Fluorescence analyses of intracellular pH revealed that fMLP uptake was accompanied by cytosolic acidification, consistent with the known function of hPepT1 as a peptide H+ cotransporter. Lumenal fMLP resulted in directed movement of neutrophils across epithelial monolayers. Solutes that inhibit hPepT1-mediated fMLP transport decreased neutrophil transmigration by approximately 50%. Conversely, conditions that enhanced the rate of hPepT1-mediated fMLP uptake (cytosolic acidification) enhanced neutrophil-transepithelial migration by approximately 70%. We conclude that hPepT1 transports fMLP and uptake of these peptide influences neutrophil-epithelial interactions. These data (a) emphasize the importance of hPepT1 in mediating intestinal inflammation, (b) raise the possibility that modulating hPepT1 activity could influence states of intestinal inflammation, and (c) provide the first evidence of a link between active transepithelial transport and neutrophil-epithelial interactions.
Adibi,
The oligopeptide transporter (Pept-1) in human intestine: biology and function.
1997, Pubmed
Adibi,
The oligopeptide transporter (Pept-1) in human intestine: biology and function.
1997,
Pubmed
Augeron,
Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate.
1984,
Pubmed
Bommakanti,
Reconstitution of a physical complex between the N-formyl chemotactic peptide receptor and G protein. Inhibition by pertussis toxin-catalyzed ADP ribosylation.
1992,
Pubmed
Boyarsky,
Superiority of in vitro over in vivo calibrations of BCECF in vascular smooth muscle cells.
1996,
Pubmed
Chadwick,
Production of peptides inducing chemotaxis and lysosomal enzyme release in human neutrophils by intestinal bacteria in vitro and in vivo.
1988,
Pubmed
Colgan,
IFN-gamma modulates CD1d surface expression on intestinal epithelia.
1996,
Pubmed
Dantzig,
Association of intestinal peptide transport with a protein related to the cadherin superfamily.
1994,
Pubmed
Dharmsathaphorn,
Established intestinal cell lines as model systems for electrolyte transport studies.
1990,
Pubmed
Fei,
Expression cloning of a mammalian proton-coupled oligopeptide transporter.
1994,
Pubmed
,
Xenbase
Ganapathy,
Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2.
1995,
Pubmed
Ganapathy,
Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2.
1997,
Pubmed
,
Xenbase
Jung,
A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion.
1995,
Pubmed
Liang,
Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization.
1995,
Pubmed
,
Xenbase
Mackenzie,
The human intestinal H+/oligopeptide cotransporter hPEPT1 transports differently-charged dipeptides with identical electrogenic properties.
1996,
Pubmed
,
Xenbase
Madara,
5'-adenosine monophosphate is the neutrophil-derived paracrine factor that elicits chloride secretion from T84 intestinal epithelial cell monolayers.
1993,
Pubmed
Madara,
ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation.
1993,
Pubmed
Marasco,
Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced by Escherichia coli.
1984,
Pubmed
McCormick,
Apical secretion of a pathogen-elicited epithelial chemoattractant activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium.
1998,
Pubmed
McCormick,
Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils.
1993,
Pubmed
McCormick,
Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils.
1995,
Pubmed
Merlin,
Recruitment of purinergically stimulated Cl- channels from granule membrane to plasma membrane.
1996,
Pubmed
Mooseker,
Organization, chemistry, and assembly of the cytoskeletal apparatus of the intestinal brush border.
1985,
Pubmed
Murphy,
The molecular biology of leukocyte chemoattractant receptors.
1994,
Pubmed
Nash,
Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers.
1987,
Pubmed
Nussberger,
Symmetry of H+ binding to the intra- and extracellular side of the H+-coupled oligopeptide cotransporter PepT1.
1997,
Pubmed
,
Xenbase
Parkos,
Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction.
1991,
Pubmed
Parkos,
Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils.
1996,
Pubmed
Saito,
Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2.
1993,
Pubmed
Steel,
Stoichiometry and pH dependence of the rabbit proton-dependent oligopeptide transporter PepT1.
1997,
Pubmed
,
Xenbase
Thwaites,
Direct assessment of dipeptide/H+ symport in intact human intestinal (Caco-2) epithelium: a novel method utilising continuous intracellular pH measurement.
1993,
Pubmed