PepT1-mediated fMLP transport induces intestinal inflammation in vivo

• Published in: American Journal of Physiology: Cell Physiology 2002-12, Vol.283 (6), p.C1795-C1800
• Main Authors: Buyse, Marion, Tsocas, Annick, Walker, Francine, Merlin, Didier, Bado, Andre
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - physiology; Carrier Proteins - physiology; Colon - drug effects; Colon - metabolism; Enteritis - chemically induced; Enteritis - pathology; Jejunum - drug effects; Jejunum - metabolism; Jejunum - pathology; Male; N-Formylmethionine Leucyl-Phenylalanine - pharmacokinetics; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Peptide Transporter 1; Peroxidase - metabolism; Rats; Rats, Wistar; Symporters
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00186.2002

1  Epithelial Pathology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322; and 2  Institut National de la Santé et de la Recherche Médicale Unité 410, Faculte de Medecine Xavier Bichat Paris, 75018 Paris, France In the present study, the effect of H + /peptide transporter (PepT1)-mediated N -formylmethionyl-leucyl-phenylalanine (fMLP) transport on inflammation in vivo in the rat small intestine, which expresses high PepT1 levels, and in the rat colon, which does not express PepT1, were investigated using myeloperoxidase (MPO) activity and histological analysis. We found that 10 µM fMLP perfusion in the jejunum for 4 h significantly increased MPO activity and altered the architecture of jejunal villi. In contrast, 10 µM fMLP perfusion in the colon for 4 h did not induce any inflammation. In addition, we have shown that 50 mM Gly-Gly alone did not affect basal MPO activity but completely inhibited the MPO activity induced by 10 µM fMLP in the jejunum. Together, these experiments demonstrate that 1 ) the differential expression of PepT1 between the small intestine and the colon plays an important role in epithelial-neutrophil interactions and 2 ) the inhibition of fMLP uptake by jejunal epithelial cells (expressing PepT1) reduces the neutrophil ability to move across the epithelium, in agreement with our previously published in vitro study. This report constitutes the first in vivo study showing the implication of a membrane transporter (PepT1) in intestinal inflammation. PepT1; N -formylmethionyl-leucyl-phenylalanine; myeloperoxidase; rat