MIP-2 secreted by epithelial cells increases neutrophil and lymphocyte recruitment in the mouse intestine.

Abstract:

BACKGROUND:Invasion of the intestinal mucosa by leucocytes is a characteristic of intestinal inflammation but the role of the epithelium in orchestrating this recruitment has not been examined in vivo. Cultured intestinal epithelial cells secrete a wide variety of chemokines, often in response to agents present in the intestinal lumen. Macrophage inflammatory protein 2 (MIP-2) is a chemokine that attracts neutrophils, and its secretion from intestinal epithelial cells is enhanced by inflammatory stimuli such as interleukin 1beta. We hypothesised that the production of MIP-2 by epithelial cells would increase leucocyte migration into the intestine. AIM:To study the effects of a chemokine secreted from intestinal epithelial cells in vivo. METHODS:MIP-2 was expressed in the mouse intestinal epithelium using an epithelial cell specific promoter from the gene encoding the intestinal fatty acid binding protein. The intestines of these transgenic mice were then analysed. RESULTS:Epithelial cells from transgenic mice expressed MIP-2 but wild-type mice did not. Neutrophil recruitment, examined by myeloperoxidase (MPO) staining and total MPO activity per unit weight of intestine, was significantly increased in transgenic mice in both the small intestine and proximal colon, and this was blocked by anti-MIP-2 antibody treatment. Both intraepithelial and lamina propria lymphocytes were also increased in transgenic mice. They showed chemotactic activity to MIP-2 in the Boyden chambers and expressed MIP-2 receptor (CXCR-2) mRNA confirmed by reverse transcription-polymerase chain reaction. CONCLUSION:These experiments are the first to show a functional role for epithelial chemokines in vivo and reveal an unexpected role for the neutrophil chemokine MIP-2 in controlling mucosal lymphocyte migration.

journal_name

Gut

journal_title

Gut

authors

Ohtsuka Y,Lee J,Stamm DS,Sanderson IR

doi

10.1136/gut.49.4.526

keywords:

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

526-33

issue

4

eissn

0017-5749

issn

1468-3288

journal_volume

49

pub_type

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