In vivo secretion of the mouse immunoglobulin G Fc fragment from rat submandibular glands.
BACKGROUND
Salivary glands have been proposed as target organs for gene therapy. They secrete endogenous, as well as transgenic proteins, in a polarized manner. Transgene-encoded regulated pathway proteins primarily follow the regulated pathway in rat salivary glands and are secreted into saliva in an exocrine manner. Conversely, constitutive pathway proteins generally are secreted more basolaterally and thus follow the endocrine route. In the present study, we studied in vivo the sorting of the mouse immunoglobulin G2b Fc fragment, which is physiologically secreted via the constitutive pathway.


METHODS
Adenoviral vectors encoding the Fc fragment and human growth hormone were delivered into rat and mouse submandibular glands in vivo to compare their serum-to-saliva distribution. We also compared the intracellular localization of the Fc fragment and growth hormone by confocal microscopy.


RESULTS
We found that the Fc fragment was secreted almost entirely into the bloodstream from rat and mouse submandibular glands via a constitutive or constitutive-like pathway. This sorting behaviour is clearly different from that of transgenic human growth hormone, which is secreted in a regulated pathway, both in neuroendocrine cells and as a transgenic protein from salivary gland cells. We also found that simultaneously expressed human growth hormone and the mouse Fc fragment do not appear to influence each other's sorting behaviour. The Fc fragment showed a primarily basal localization, whereas growth hormone showed an apical localization, in rat submandibular gland acinar cells.


CONCLUSIONS
The results obtained in the present study indicate that the mouse Fc fragment is a useful model protein for examining the basolateral versus apical secretory pathways employed by transgenic secretory proteins in salivary glands.
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. gabor.z.racz@gmail.com
Gabor Z
GZ
Racz
Paola
P
Perez-Riveros
Janik
J
Adriaansen
Changyu
C
Zheng
Bruce J
BJ
Baum
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000276:immunology / Q000378:metabolism; D019076:Transgenes
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D019382:Human Growth Hormone