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Publication : MUC1 cell surface mucin is a critical element of the mucosal barrier to infection.

First Author  McAuley JL Year  2007
Journal  J Clin Invest Volume  117
Issue  8 Pages  2313-24
PubMed ID  17641781 Mgi Jnum  J:123962
Mgi Id  MGI:3720276 Doi  10.1172/JCI26705
Citation  McAuley JL, et al. (2007) MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest 117(8):2313-24
abstractText  Cell surface mucin glycoproteins are highly expressed by all mucosal tissues, yet their physiological role is currently unknown. We hypothesized that cell surface mucins protect mucosal cells from infection. A rapid progressive increase in gastrointestinal expression of mucin 1 (Muc1) cell surface mucin followed infection of mice with the bacterial pathogen Campylobacter jejuni. In the first week following oral infection, C. jejuni was detected in the systemic organs of the vast majority of Muc1(-/-) mice but never in Muc1(+/+) mice. Although C. jejuni entered gastrointestinal epithelial cells of both Muc1(-/-) and Muc1(+/+) mice, small intestinal damage as manifested by increased apoptosis and enucleated and shed villous epithelium was more common in Muc1(-/-) mice. Using radiation chimeras, we determined that prevention of systemic infection in wild-type mice was due exclusively to epithelial Muc1 rather than Muc1 on hematopoietic cells. Expression of MUC1-enhanced resistance to C. jejuni cytolethal distending toxin (CDT) in vitro and CDT null C. jejuni showed lower gastric colonization in Muc1(-/-) mice in vivo. We believe this is the first in vivo experimental study to demonstrate that cell surface mucins are a critical component of mucosal defence and that the study provides the foundation for exploration of their contribution to epithelial infectious and inflammatory diseases.
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