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(American Journal of Pathology. 2002;161:771-779.)
© 2002 American Society for Investigative Pathology

Short Communication

Enteric Expression of the Integrin _vß₆ Is Essential for Nematode-Induced Mucosal Mast Cell Hyperplasia and Expression of the Granule Chymase, Mouse Mast Cell Protease-1

Pamela A. Knight^*, Steven H. Wright^*, Jeremy K. Brown^*, Xiaozhu Huang, Dean Sheppard and Hugh R. P. Miller^*

From the Department of Veterinary Clinical Studies,^* University of Edinburgh, Midlothian, Scotland; and the Lung Biology Center, University of California, San Francisco, California

The immunoregulatory cytokine transforming growth factor (TGF)-ß₁ 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 _vß₆ mediates local activation of TGF-ß₁ in the lung and ß₆^-/- mice exhibit exaggerated pulmonary inflammation, but their response to inflammatory stimuli in the gut has not been investigated. We found that both ß₆ and TGF-ß₁ 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 ß₆^-/- 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-ß₁, these data indicate that in the absence of _vß₆ epithelially expressed TGF-ß₁ 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.

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