Abstract 1080: Constricture of the Excretory Duct in Parotid Salivary Glands of a Mouse Model of Sjögren’s Syndrome that Exhibits Decreased Salivary Flow
Thomas Grader-Beck
Authors
Shannon M. Maier, Biji T. Kurien, Anil D'Souza1, Sima Asfa2, R. Hal Scofield2
Background
This study investigated possible mechanisms of decreased salivary flow in a well-established mouse model of Sjogren’s syndrome, e.g. immunization of BALB/c mice with Ro274 peptide. In particular, the question was addressed whether morphological changes within the salivary gland ducts are responsible for decreased salivary flow and/or whether the effects are mediated by other factors such as infiltrate blockade or decreased salivary production.
Methods:
BALB/c mice were immunized with Ro 274 peptide in CFA or with vehicle alone. Serum was collected for detection of anti-Ro and anti-Ro274-specific antibodies. Pilocarpine-induced salivary flow volume was assessed to measure glandular function. Parotid salivary glands were embedded in paraffin for Hematoxylin and Eosin (HE) staining or embedded in LR White resin for electron microscopy. HE-stained sections were examined for infiltrating cells and gross morphological changes. Parotid gland ultrastructure was evaluated by electron microscopy.
Results:
BALB/c mice immunized with Ro274 peptide had significant titers of anti-Ro and anti-Ro274 antibodies compared to vehicle-immunized mice. HE sections of parotid gland from Ro274-immunized mice had mononuclear infiltration with foci primarily around the acinar ducts and vessels that were absent in control mice. Decreased salivary flow in Ro274-immunized mice compared to controls indicates Ro274 involvement in the functional impairment of salivary function. Ultramicrographs of the excretory ducts showed that immunization of mice with Ro274 peptide led to a significant constricture of the duct, approximately 26-fold smaller than that of control mice. EM images taken within the parotid glands also revealed the presence of infiltrating cells in capillaries and intralobular spaces.
Conclusions:
Ultrastructural analysis of parotid salivary glands from Ro274-immunized mice with antibodies to Ro and Ro274 that have decreased salivary flow and cellular infiltrates also demonstrate significant constricture of the acinar ducts that may play a role in the functional impairment of the gland.
Editorial Comment
Maier et al. report in their study on the potential novel finding that constriction of secretory ducts may play a role in the pathogenesis of hyposalivation in Sjogren’s syndrome. Other findings, including a potential role of cellular infiltrates and decreased saliva production have been described extensively in the past. It remains unclear whether it is truly active constriction of the ducts or whether the marked decrease in duct diameter of Sjogren’s mice is a consequence of decreased saliva production. Mechanism of active duct constriction may include autoantibodies that exhibit norepinephrine-like effects. Targeting salivary gland duct constriction may represent a novel therapeutic apporoach for Sjogren’s syndrome.
