Enteric expression of the integrin αvβ6 is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1

• Published in: The American journal of pathology Vol. 161; no. 3; pp. 771 - 779
• Main Authors: KNIGHT, Pamela A, WRIGHT, Steven H, BROWN, Jeremy K, XIAOZHU HUANG, SHEPPARD, Dean, MILLER, Hugh R. P
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Investigative Pathology 01.09.2002
• Subjects: Biological and medical sciences; Experimental helminthic diseases. Models; Helminthic diseases; Infectious diseases; Medical sciences; Parasitic diseases; Short Communication; Immunohistochemistry; Hyperplasia; Transgenic animal; Integrin; Intestinal disease; Serine endopeptidases; Enzyme; Rodentia; Cytokine; Gut; Cell adhesion molecule; Inflammation; Parasitosis; Gene expression; Helminthiasis; Chymase; Infection; Pathology; Peptidases; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Nematode disease; Digestive diseases; Hydrolases; Mast cell; Transforming growth factor β1; Molecular biology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64236-8

The immunoregulatory cytokine transforming growth factor (TGF)-β 1 is secreted as a biologically inactive complex with latency-associated peptide, which must be modified by local factors to expose the functionally active cytokine. The epithelial integrin α v β 6 mediates local activation of TGF-β 1 in the lung and β 6 −/− mice exhibit exaggerated pulmonary inflammation, but their response to inflammatory stimuli in the gut has not been investigated. We found that both β 6 and TGF-β 1 are constitutively expressed in the jejunal epithelial compartment in uninfected mice and during infection with the intestinal nematode Nippostrongylus brasiliensis . We also present data showing that β 6 −/− mice are seriously compromised in their ability to mount a mucosal mast cell response after infection, and there is a significant reduction in the expression and systemic release of the granule chymase, mouse mast cell protease-1. Because in vitro expression of this chymase is regulated by TGF-β 1 , these data indicate that in the absence of α v β 6 epithelially expressed TGF-β 1 may not be activated, with a consequent absence of expression of mouse mast cell protease-1 and down-regulation of the mucosal mast cell response.