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© The Rockefeller University Press, 0022-1007/1999/10/915/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 915-922

Absence of Epithelial Immunoglobulin A Transport, with Increased Mucosal Leakiness, in Polymeric Immunoglobulin Receptor/Secretory Component–deficient Mice

Finn-Eirik Johansena, Marcela Peknab, Inger Natvig Norderhauga, Bjørn Hanebergc, Max Albert Hietalab, Peter Krajcia, Christer Betsholtzb, and Per Brandtzaega
a Laboratory of Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway
b Department of Medical Biochemistry, University of Göteborg, SE-405 30 Göteborg, Sweden
c Department of Vaccinology, National Institute of Public Health, N-0462 Oslo, Norway

Correspondence to: Finn-Eirik Johansen, Institute of Pathology, University of Oslo, Rikshospitalet, N-0027 Norway. Tel:47-2286-8607 Fax:47-2211-2261 E-mail:f.e.johansen{at}labmed.uio.no.

Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Paracellular passive external transfer of systemic and locally produced antibodies also provides mucosal protection, making the biological importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The knockout mice were of normal size and fertility but had increased serum IgG levels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function in the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins. Thus, SIgA did not appear to be essential for health under the antigen exposure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Production of SIgA might therefore be a variable in the initiation of human immunopathology such as inflammatory bowel disease or gluten-sensitive enteropathy.

Key Words: IgA, secretory, receptors, polymeric immunoglobulin, secretory component, immunity, mucosal, mice, knockout


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