Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjogren's syndrome patients

Patients with Sjogren's syndrome (SS) suffer from deficient secretion of sa liva due to an autoimmune destruction of salivary glands, however, glandula r dysfunction also occurs without destruction. Based upon its abnormal dist ribution in SS salivary glands, a potential role for the water channel prot ein aquaporin-5 (AQP5) is proposed in the pathogenesis of SS. The immunohis tochemical distribution of AQP5 was compared in minor salivary gland biopsi es obtained from women after informed consent: primary SS (53.2 +/- 14 year s old, n = 10), healthy volunteers (46.2 +/- 17 years old, n = 10), patient s with sarcoidosis (37 and 48 years old), and patients with non-specific si aloadenitis (54 and 61 years old). Biopsies from normal subjects revealed A QP5 primarily at the apical membrane of the salivary gland acinus. In contr ast, biopsies from SS patients revealed AQP5 primarily at the basal membran es of the acinus. The AQP5 distribution in biopsies from patients with othe r dry mouth disorders, such as non-specific sialoadenitis or sarcoidosis, w as similar to biopsies from control subjects. Computer-assisted microscopy was performed to quantitatively evaluate AQP5 distribution in the immunorea ctive acini of both SS and control subjects. Biopsies from SS patients had higher labeling indices (percentage of acinus area immunoreactive for AQPS) at the basal membrane when compared with biopsies from control subjects. I n contrast, biopsies of SS patients exhibited lower labeling indices at the apical membrane when compared with biopsies from control subjects. To veri fy the specificity of the AQPS antibody, Western blot analysis was performe d on membranes from Xenopus oocytes injected with AQP5 cRNA or on membranes from minor salivary glands of control subjects and SS patients, in each ca se, the immunoblots had a 27 kd band, corresponding to the expected molecul ar weight of AQP5. Abnormal distribution of AQP5 in salivary gland acini is likely to contribute to the deficiency of fluid secretion, which is a defi ning feature of Sjogren's syndrome.