INAPPROPRIATE APOPTOSIS OF SALIVARY AND LACRIMAL GLAND EPITHELIUM OF IMMUNODEFICIENT NOD-SCID MICE

Objective The lesion in Sjogren's syndrome consists of lymphocytic inf iltration and has a pathology characteristic of the potential apoptoti c death of salivary gland secretory epithelial cells. To examine the r ole of the glandular epithelial cells in the pathogenesis of autoimmun e exocrinopathy, we studied Fas and Fas ligand (FasL) expression and q uantitated the levels of apoptosis in salivary and lacrimal glands fro m NOD and NOD-scid mice, an animal model that develops a Sjogren's syn drome-like pathology. Methods The parotid, submandibular and lacrimal tissues of NOD, NOD-scid, and BALB/c mice were evaluated by immunohist ochemical analysis for the expression of mu and Fast. Nuclear fragment ation of DNA from the epithelial cells of exocrine tissues was evaluat ed by the terminal UTP nucleotide end labeling method (TUNEL). Messeng er RNA was isolated from 8 and 18 week old mice and was analyzed by th e reverse transcription-polymerase chain reaction (RT-PCR) for the exp ression of Fas and FasL. Results We found suggestive evidence that apo ptosis of the secretory epithelial cells occurs in both NOD and NOD-so ld mice despite the lack of T- and B-lymphocytes in the latter. FasL m RNA and cell surface protein were expressed in salivary and lacrimal g land epithelial cells from 8 and 18 week old NOD, NOD-scid, and BALB/c mice. Fas protein and mRNA were expressed only in the exocrine glands from 18 week old NOD and NOD-sold mice. Glandular secretory epithelia l cell apoptosis was elevated in both NOD and NOD-scid mice, however; there was little evidence of apoptosis in the control strain of BALB/c mice. Conclusion These results suggest a potential apoptotic process dependent on Fas:FasL interactions occurring in NOD-scid glandular sec retory epithelial cells in the absence of lymphocytic infiltration.