Characterization of CFTR High Expresser (CHE) cells of the small intestine

Abstract

The CHE cells express 8‐fold higher levels of the CFTR Clchannel compared to neighboring enterocytes, and were first identified by our laboratory (Ameen et al 1995, Gastroenterology 108:1016). We used double label immunofluorescence microscopy to further study these enigmatic epithelial cells in rat. CHE cells are found in duodenum, most frequent in proximal jejunum, and absent in ileum and colon. CFTR abundance increases in CHE cells along the crypt‐villus axis. The basolateral Cl− transporter NKCC1 was detected at similar levels in CHE cells and neighboring enterocytes at steady state. Microvilli were shorter in CHE cells, with low levels of Myosin1A ‐ a villus enterocyte specific motor that retains sucrase/isomaltase (SI) in the brush border membrane (BBM). CHE cells lacked absorptive villus enterocyte BBM proteins including: NHE3, SLC26A6 (PAT1) and SI. High levels of the vATPase proton pump were observed in the apical domain of CHE cells. Levels of Syntaxin 3, NHERF1, and Na‐K‐ATPase were similar to that of neighboring enterocytes. cAMP or carbachol stimulation robustly increased apical CFTR and basolateral NKCC1 disproportionately in CHE cells relative to neighboring enterocytes. These data strongly argue for a specialized role of CHE cells in Cl−‐mediated “high‐volume” fluid secretion in the proximal small intestine.NIDDK Grants R01‐DK‐077065 (N.A.) and P30 DK‐34989 (Yale Liver Center).