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Research Article Free access | 10.1172/JCI115156

In vitro model of intestinal crypt abscess. A novel neutrophil-derived secretagogue activity.

S Nash, C Parkos, A Nusrat, C Delp, and J L Madara

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Find articles by Nash, S. in: PubMed | Google Scholar

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Find articles by Parkos, C. in: PubMed | Google Scholar

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Find articles by Nusrat, A. in: PubMed | Google Scholar

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Find articles by Delp, C. in: PubMed | Google Scholar

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Find articles by Madara, J. in: PubMed | Google Scholar

Published April 1, 1991 - More info

Published in Volume 87, Issue 4 on April 1, 1991
J Clin Invest. 1991;87(4):1474–1477. https://doi.org/10.1172/JCI115156.
© 1991 The American Society for Clinical Investigation
Published April 1, 1991 - Version history
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Abstract

In order to model crypt abscesses, a histological finding which correlates with disease activity in intestinal inflammation, human polymorphonuclear leukocytes (PMN) were layered onto monolayers of the human intestinal epithelial cell line T84, a crypt-like epithelium which is capable of Cl- secretion. Such PMN-epithelial interaction had no substantial effect on monolayer integrity or function. However, when PMN were stimulated by conditions including those present naturally in the human colonic lumen, monolayers responded with a bumetanide-sensitive short circuit current (Isc) indicative of Cl- secretion, the basis of secretory diarrhea. This Isc response was induced by a neutrophil-derived secretagogue (NDS), which was only active when applied to the luminal surface of monolayers and did not require PMN-epithelial contact. NDS activity is resistant to boiling, acid, and trypsin and passes a 500 nominal mol wt cutoff filter. NDS activity is not secondary to the respiratory burst products O2- or H2O2 and does not appear to be a myeloperoxidase product. We speculate NDS elicited Cl- secretion may contribute to the secretory diarrhea seen in patients with intestinal inflammation and crypt abscesses.

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