hPepT1 mediates bacterial tripeptide fMLP uptake in human monocytes
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Here, we examined hPepT1 expression in the monocytic cell line, KG-1. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that hPepT1 is expressed in KG-1 cells, while cDNA cloning and direct sequencing confirmed the sequence of KG-1 hPepT1 (accession number, AY634368). Immunoblotting of cell lysates from KG-1 cells or macrophages isolated from human peripheral blood revealed a approximately 100 kDa immunoreactive band mainly present in the membrane fraction. Uptake experiments showed that the transport of 20 microM radiolabeled Gly-Sarcosine ([14C]Gly-Sar) in KG-1 cells was Na+, Cl- dependent and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS)-sensitive. In addition, hPepT1 activity was likely to be coupled to a Na+/H+ exchanger, as evidenced by the fact that [14C]Gly-Sar uptake was not affected by the absence of Na+ when cells were incubated at low pH (5.2). Interestingly, hPepT1-mediated transport was reduced in KG-1 cells incubated at low pH as it was also observed in nonpolarized Caco2-BBE cells. This pattern of pH-dependence is due to a disruption of the driving force of hPepT1-mediated transport events. This was supported by our finding that nonpolarized cells, Caco2-BBE cells and KG-1 cells, have an increased permeability to H+ when compared to polarized Caco2-BBE cells. Finally, we showed that hPepT1 is responsible for transporting fMLP into undifferentiated and differentiated (macrophage-like) KG-1 cells. Together, these results show that hPepT1 is expressed in nonpolarized immune cells, such as macrophages, where the transporter functions best at the physiological pH 7.2. Furthermore, we provide evidence for hPepT1-mediated fMLP transport, which might constitute a novel immune cell activation pathway during intestinal inflammation.
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Signals that originate from luminal micro-organisms and influence the gut epithelium involve well-characterized mechanisms, such as Toll-like receptor signaling and signaling by bipeptides or tripeptides.
“Signals that originate from luminal micro-organisms and influence the gut epithelium have been studied extensively, and involve well-characterized mechanisms, such as Toll-like receptor signaling48,49 and signaling by bipeptides or tripeptides, such as N-formylmethionyl–leucyl–phenylalanine.50”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [50]
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Thomas, J. A., Buchsbaum, R., Zimniak, A., & Racker, E. (1979) · Biochemistry · doi:10.1021/bi00578a012 · Cited by 2,132 · see citing works
FRACTURE FACES OF ZONULAE OCCLUDENTES FROM "TIGHT" AND "LEAKY" EPITHELIA
Claude, P., & Goodenough, D. A. (1973) · The Journal of Cell Biology · doi:10.1083/jcb.58.2.390 · Cited by 1,094 · see citing works
Smythies, L. E., Sellers, M. T., Clements, R. H., Mosteller‐Barnum, M., Meng, G., Benjamin, W. H., Orenstein, J. M., & Smith, P. D. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200519229 · Cited by 924 · see citing works
Molecular and Integrative Physiology of Intestinal Peptide Transport
Daniel, H. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.032102.144149 · Cited by 602 · see citing works
Formyl-peptide receptors revisited
Le, Y., MURPHY, P., & Wang, J. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02316-5 · Cited by 600 · see citing works
Claude, P. (1978) · The Journal of Membrane Biology · doi:10.1007/bf01870332 · Cited by 569 · see citing works
Acute Myelogenous Leukemia: A Human Cell Line Responsive to Colony-Stimulating Activity
Koeffler, H. P., & Golde, D. W. (1978) · Science · doi:10.1126/science.306682 · Cited by 525 · see citing works
Marasco, W. A., Phan, S. H., Krutzsch, H. C., et al. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)91029-x · Cited by 524 · see citing works
Human myeloid leukemia cell lines: a review
Koeffler, H., & Golde, D. (1980) · Blood · doi:10.1182/blood.v56.3.344.344 · Cited by 349 · see citing works
Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation
Chamaillard, M., Girardin, S. E., Viala, J., & Philpott, D. J. (2003) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00304.x · Cited by 344 · see citing works
Smith, P. D., Smythies, L. E., Mosteller‐Barnum, M., Sibley, D. A., Russell, M. W., Merger, M., Sellers, M. T., Orenstein, J. M., Shimada, T., Graham, M. F., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.5.2651 · Cited by 327 · see citing works
Vavricka, S. R., Musch, M. W., Chang, J. E., Nakagawa, Y., Phanvijhitsiri, K., Waypa, T. S., Merlin, D., Schneewind, O., & Chang, E. B. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.07.024 · Cited by 243 · see citing works
Self-citationImmuno-Localization of H+/Peptide Cotransporter in Rat Digestive Tract
Ogihara, H., Saito, H., Shin, B., Terada, T., Takenoshita, S., Nagamachi, Y., Inui, K., & Takata, K. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0493 · Cited by 226 · see citing works
Buyse, M., Berlioz, F., Guilmeau, S., Tsocas, A., Voisin, T., Péranzi, G., Merlin, D., Laburthe, M., Lewin, M. J. M., Rozé, C., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13219 · Cited by 224 · see citing works
Self-citationRegulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease
Adibi, S. A. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00056.2003 · Cited by 222 · see citing works
Ziegler, T. R., Fernández‐Estívariz, C., Gu, L. H., et al. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.5.922 · Cited by 200 · see citing works
Merlin, D., Si‐Tahar, M., Sitaraman, S. V., Eastburn, K., Williams, I. R., Liu, X., Hediger, M. A., & Madara, J. (2001) · Gastroenterology · doi:10.1053/gast.2001.24845 · Cited by 197 · see citing works
Self-citationInherited disorders of human Toll‐like receptor signaling: immunological implications
Ku, C., Yang, K., Bustamante, J. C., Puel, A., von Bernuth, H., Filipe‐Santos, O., Lawrence, T. C., Chang, H., Al‐Mousa, H., Pïcard, C., et al. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00235.x · Cited by 132 · see citing works
Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1
Groneberg, D. A., Döring, F., Eynott, P. R., et al. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.3.g697 · Cited by 130 · see citing works
CHADWICK, V. S., Mellor, D. M., Myers, D. B., et al. (1988) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365528809093861 · Cited by 122 · see citing works
Buyse, M., Sitaraman, S. V., Liu, X., Bado, A., & Merlin, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203281200 · Cited by 119 · see citing works
Self-citationThwaites, D. T., Kennedy, D. J., Raldúa, D., et al. (2002) · Gastroenterology · doi:10.1053/gast.2002.32992 · Cited by 118 · see citing works
Schenk, M., Bouchon, A., Birrer, S., Colonna, M., & Mueller, C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.1.517 · Cited by 114 · see citing works
Merlin, D., Steel, A., Gewirtz, A. T., Si‐Tahar, M., Hediger, M. A., & Madara, J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4179 · Cited by 97 · see citing works
Self-citationPepT1-mediated fMLP transport induces intestinal inflammation in vivo
Buyse, M., Tsocas, A., Walker, F., Merlin, D., & Bado, A. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00186.2002 · Cited by 76 · see citing works
Self-citationInnate immunity and mucosal bacterial interactions in the intestine
Eckmann, L. (2004) · Current Opinion in Gastroenterology · doi:10.1097/00001574-200403000-00006 · Cited by 71 · see citing works
Sai, Y., Tamai, I., Sumikawa, H., Hayashi, K., Nakanishi, T., Amano, O., Numata, M., Iseki, S., & Tsuji, A. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00778-8 · Cited by 61 · see citing works
ADAM-15 inhibits wound healing in human intestinal epithelial cell monolayers
Charrier, L., Yan, Y., Driss, A., LABOISSE, C. L., Sitaraman, S. V., & Merlin, D. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00262.2004 · Cited by 56 · see citing works
Self-citationSaksena, S., Gill, R. K., Tyagi, S., Alrefai, W. A., Sarwar, Z. U., Ramaswamy, K., & Dudeja, P. K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411553200 · Cited by 46 · see citing works
Buyse, M., Charrier, L., Sitaraman, S. V., et al. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63555-9 · Cited by 44 · see citing works
Self-citationEfflux properties of basolateral peptide transporter in human intestinal cell line Caco-2
Irie, M., Terada, T., Okuda, M., & Inui, K. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-004-1326-x · Cited by 43 · see citing works
Saito, H., Motohashi, H., Mukai, M., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7129 · Cited by 34 · see citing works
H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.
Vyas, J. M., Rodgers, J. R., & Rich, R. R. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.5.1817 · Cited by 25 · see citing works
Polarity of alveolar epithelial cell acid-base permeability
Joseph, D., Tirmizi, O., Zhang, X., et al. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00330.2001 · Cited by 19 · see citing works
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Principles and clinical implications of the brain-gut-enteric microbiota axis
Rhee, S. H., Pothoulakis, C., & Mayer, E. A. (2009) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.35 · Cited by 1,342 · see citing works
“and signaling by bipeptides or tripeptides, such as N -formylmethionyl–leucyl–phenylalanine”
- Authors
- Charrier, L., Driss, A., Yan, Y., Nduati, V., Klapproth, J.-M., Sitaraman, S. V., & Merlin, D.
- Affiliations
- Emory University (US)
- Corresponding author
- Merlin, Didier
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 86
- Issue
- 5
- Pages
- 490-503
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W1515316094
- Cited by
- 52
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 5
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation of America (R24-DK-064399)
- Crohn's and Colitis Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK064399, K08DK062899, DK 064399, DK 061941, DK062899, DK064711, R01DK064711)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- hPEPT1, peptide transporters, fMLP, human monocytes, macrophages, KG-1 cells, Na+/H+ exchanger, pH-dependent transport, intestinal inflammation, immune cell activation, Caco-2 cells
- MeSH terms
- Peptide Transporter 1, Biological Transport, Active, Cell Differentiation, Cell Line, Cell Membrane Permeability, Dipeptides, Humans, Hydrogen-Ion Concentration, Macrophages, Monocytes, N-Formylmethionine Leucyl-Phenylalanine, Protons, Sodium, Cell Polarity, 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid, Caco-2 Cells, Symporters
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