First published November 2, 2009 - More info
The mechanisms underlying mucus-associated pathologies in cystic fibrosis (CF) remain obscure. However, recent studies indicate that CF transmembrane conductance regulator (CFTR) is required for bicarbonate (HCO3–) transport and that HCO3– is critical for normal mucus formation. We therefore investigated the role of HCO3– in mucus secretion using mouse small intestine segments ex vivo. Basal rates of mucus release in the presence or absence of HCO3– were similar. However, in the absence of HCO3–, mucus release stimulated by either PGE2 or 5-hydroxytryptamine (5-HT) was approximately half that stimulated by these molecules in the presence of HCO3–. Inhibition of HCO3– and fluid transport markedly reduced stimulated mucus release. However, neither absence of HCO3– nor inhibition of HCO3– transport affected fluid secretion rates, indicating that the effect of HCO3– removal on mucus release was not due to decreased fluid secretion. In a mouse model of CF (mice homozygous for the most common human CFTR mutation), intestinal mucus release was minimal when stimulated with either PGE2 or 5-HT in the presence or absence of HCO3–. These data suggest that normal mucus release requires concurrent HCO3– secretion and that the characteristically aggregated mucus observed in mucin-secreting organs in individuals with CF may be a consequence of defective HCO3– transport.
Mary Abigail S. Garcia, Ning Yang, Paul M. Quinton
Original citation: J. Clin. Invest.119:2613–2622 (2009). doi:10.1172/JCI38662.
Citation for this corrigendum: J. Clin. Invest.119:3497 (2009). do:10.1172/JCI38662C1.
During the preparation of the manuscript, Yasutada Akiba and Jonathan D. Kaunitz’s names were inadvertently omitted from Acknowledgments. The correct Acknowledgments section appears below.
This work was supported by the Nancy Olmsted Trust (NIH-NHLB RO1-HL084042) and the Cystic Fibrosis Foundation. The authors thank Guillermo Flores-Delgado for his assistance with assays and with mutant mice genotyping, and Kirk Taylor for technical assistance. Statistical assistance was provided in part by NIH grant MO1 RR-00827 for the UCSD General Clinical Research Center. The authors thank Yasutada Akiba and Jonathan D. Kaunitz (David Geffen School of Medicine, UCLA, Los Angeles, California, USA) for their crucial instruction in conducting the PAS dot-blot method for measuring mucus content in intestinal perfusates (Akiba, Y., Guth, P.H., Engel, E., Nastaskin, I., Kaunitz, J.D. 2000. Dynamic regulation of mucus gel thickness in rat duodenum. Am. J. Physiol. Gastrointest. Liver Physiol.279:G437–G447).
The authors regret the error.