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This Article Full Text Full Text (PDF) Supplemental Movies All Versions of this Article: 292/4/E1122    most recent 00381.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Mircheff, A. K. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Mircheff, A. K.

Elevated prolactin redirects secretory vesicle traffic in rabbit lacrimal acinar cells

¹Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles; ²Division of Biomedical Sciences, University of California, Riverside, California; ³Unité Génomique et Physiologie de la Lactation, Institut National de Recherche Agronomique, Jouy-en-Josas, France; ⁴Department of Ophthalmology, Keck School of Medicine; ⁵Department of Pharmaceutical Sciences, School of Pharmacy; and ⁶Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California

Submitted 31 July 2006 ; accepted in final form 1 December 2006

During pregnancy, lymphocytes infiltrating the rabbit lacrimal gland disperse to the interacinar space from their normal focal concentrations, basal fluid secretion decreases, pilocarpine-induced fluid secretion increases, and stimulated fluid protein concentration decreases. Ductal epithelial cell prolactin (PRL) content increases and redistributes from the apical to the basal-lateral cytoplasm. A replication-incompetent adenovirus vector for rabbit PRL (AdPRL) was used to test the hypothesis that increased intracrine/autocrine PRL signaling alters secretory protein traffic in an ex vivo lacrimal acinar cell model. AdPRL had no discernable influence on microtubules or actin microfilaments or their responses to carbachol (CCh). Endogenous and transduced PRLs exhibited similar, nonpolarized, punctate distributions. Cells secreted PRL consititutively and at increased rates in response to CCh. In contrast, constitutive secretion of -hexosaminidase was negligible, suggesting that the constitutive pathway for PRL is relatively inaccessible to typical secretory proteins. AdPRL had no significant effect on total secretion of -hexosaminidase or syncollin-green fluorescent protein (GFP), a chimeric secretory protein construct. However, it reversed the polarized distributions of vesicles containing rab3D and syncollin-GFP. Live-cell imaging indicated that AdPRL redirected CCh-dependent syncollin-GFP exocytosis from the apical plasma membrane to the basal-lateral membrane. Elevated concentrations of exogenous rabbit PRL in the ambient medium elicited similar changes. These observations suggest that elevated PRL, as occurs in the physiological hyperprolactinemia of pregnancy, induces lacrimal epithelial cells to express a mixed exocrine/endocrine phenotype that secretes fluid to the acinus-duct lumen but secretes proteins to the underlying tissue space. This phenotype may contribute to the pregnancy-associated immunoarchitecture.

ocular surface; mucosal immunity; pregnancy; Sjögren's syndrome