Differential Expression of Adenylyl Cyclase mRNAs in Lacrimal Glands of NZB/NZW and NOD Pre-Autoimmune Mice

  • Michele A. Meneray
  • Thomas E. Lallier
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 506)


Sjögren’s Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands. The disease is most prevalent in postmenopausal women who exhibit salivary and lacrimal insufficiencies resulting in dry mouth and dry eye. Diagnosis of SS is variously dependent upon the detection of anti-Ro (SS-A), anti-La (SS-B) and antinuclear (ANA) autoantibodies, as well as rheumatoid factor. Biopsies of the salivary and lacrimal glands of SS patients typically reveal periductal and perivascular lymphocytic infiltrates that are predominated by CD4+ T and B lymphocytes1–6. Emerging theories of the pathogenesis of SS postulate the disease proceeds in stages with the first stage characterized by an intrinsic failure of the secretory epithelial cells7–12. Successive stages include the autoimmune response in the lacrimal and salivary glands initiated by the target cells themselves. The final stage is seen as one in which immune-mediated destruction of the secretory architecture of the cell, as well as of the nerve fibers innervating the gland, occurs.


Ocular Surface Lacrimal Gland Conjunctival Epithelium Keratoconjunctivitis Sicca Conjunctival Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Fox, R.I. 1996. Clinical features, pathogenesis, and treatment of Sjögren’s syndrome. Curr. Opinion Rheum. 8:438–445.CrossRefGoogle Scholar
  2. 2.
    Fox, R.I., Törnwall, J., Maruyama, T. and Stern, M. 1998. Evolving concepts of diagnosis, pathogenesis, and therapy of Sjögren’s syndrome. Curr. Opinion Rheum. 10:446–456.CrossRefGoogle Scholar
  3. 3.
    Meilof, J.F. and Smeenk, R.J.T. 1992. Autoantibodies and their target antigens in Sjögren’s syndrome. Neth. J. Med. 40:140–147.PubMedGoogle Scholar
  4. 4.
    Nasu, M., Matsubara, O. and Yamamoto, H. 1984. Post-mortem prevalence of lymphocytic infiltration of the lacrymal gland: a comparative study in autoimmune and non-autoimmune diseases. Journal of Pathology. 143:11–15.CrossRefPubMedGoogle Scholar
  5. 5.
    Chomette, G., Auriol, M. and Liotet, S. 1986. Ultrastructural study of the lacrimal gland in a case of Sjögren’s syndrome. Scand J. Rheumatology. 61:71–75.Google Scholar
  6. 6.
    Bodeutsch, C., deWilde, P.C.M., Kater, L., Hené, R.J. van den Hoogen, F.H.J., van de Putte, L.B.A. and Vooijs, G.P. 1992. Labial salivary gland biopsy in Sjögren’s syndrome. Neth. J. Med. 40:148–157.PubMedGoogle Scholar
  7. 7.
    Talal, N. 1986. Recent developments in the immunology of Sjögren’s syndrome (autoimmune exocrinopathy). Scand. J. Rheumatology. 61:76–82.Google Scholar
  8. 8.
    Mircheff, A.K., Gierow, J.P. and Wood, R.L. 1994. Autoimmunity of the lacrimal gland. Int. Ophthalmol. Clin: Dry Eye. 34:1–18.CrossRefGoogle Scholar
  9. 9.
    Ogawa, N., Dang, H. and Talal, N. 1995. Apoptosis and autoimmunity. J. Autoimmun. 8:1–19.CrossRefPubMedGoogle Scholar
  10. 10.
    Anaya, J.M. and Talal, N. 1999. Sjögren’s syndrome comes of age. Semin. Arthritis. Rheum. 28:355–359.CrossRefPubMedGoogle Scholar
  11. 11.
    Humphreys-Beher, M.G., Peck, A.B., Dang, H. and Talal, N. 1999. The role of apoptosis in the initiation of the autoimmune response in Sjögren’s syndrome. Clin. Exp. Immunol. 116:383–387.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Humphreys-Beher, M.G., Brayer, J., Yamachika, S., Peck, A.B. and Jonsson, R. 1999. An alternative perspective to the immune response in autoimmune exocrinopathy: induction of functional quiescence rather than destructive autoaggression. Scand. J. Immunol. 49:7–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Saito, I. 1994. Possible mechanisms of cellular activation and tissue destruction in Sjögren’s syndrome. Int. Ophthalmol. Clin: Dry Eye. 13:137–143.CrossRefGoogle Scholar
  14. 14.
    Andoh, Y., Shimura, S., Sawai, T., Sasaki, H., Takishima, T. and Shirato, K. 1993. Morphometric analysis of secretory glands in Sjögren’s Syndrome. Am. Rev. Respir. Dis. 148:1358–1362.CrossRefPubMedGoogle Scholar
  15. 15.
    Bacman, S., Leiros, C.P., Sterin-Borda, L., Hubscher, O., Arana, R. and Borda, E. 1998. Autoantibodies against lacrimal gland M3 muscarinic acetylcholine receptors in patients with primary Sjögren’s syndrome. Invest. Ophthalmol. Vis. Sci. 39:151–156.PubMedGoogle Scholar
  16. 16.
    Tornwall, J., Konttinen, Y.T., Hietanen, J., Sorsa, T., Hukkanen, M. and Uusitalo, H. 1995. VIP in salivary glands in Sjögren’s syndrome. Br. J. Rheumatol. 34:891–893.CrossRefPubMedGoogle Scholar
  17. 17.
    Stern, M.E., Beuerman, R.W., Fox, R.I., Gao, J., Mircheff, A.K. and Pflugfelder, S.C. 1998. A unified theory of the role of the ocular surface in dry eye. Adv. Exp., Med. Biol. 438:643–651.CrossRefGoogle Scholar
  18. 18.
    Jabs, D.A., Enger, C. and Pendergast, R.A. 1991. Murine models of Sjögren’s syndrome: evolution of the lacrimal gland inflammatory lesions. Invest. Ophthamol. Vis. Sci. 32(2):371–380.Google Scholar
  19. 19.
    Humphreys-Beher, M.G., Hu, Y. Nakagawa, Y., Wand, P-L. and Purushotham, K.R. 1994. Utilization of the non-obese diabetic (nod) mouse as an animal model for the study of secondary Sjögren’s syndrome. Adv. Exp. Med. Biol. 350:631–636.CrossRefPubMedGoogle Scholar
  20. 20.
    Jabs, D.A. and Prendergast, R.A. 1994. Murine models of Sjögren’s syndrome. Adv. Exp. Med. Biol. 350:623–630.CrossRefPubMedGoogle Scholar
  21. 21.
    Robinson, C., Cornelius, J., Bounous, D., Yamatomo, H., Humphreys-Beher, M. and Peck, A. 1998. Characterization of the changing lymphocytic population and cytokine expression in the exocrine tissues of autoimmune NOD mic. Autoimmunity. 27:29–44.CrossRefPubMedGoogle Scholar
  22. 22.
    Yamamoto, H., Sims, N., Macauyley, S., Nguyen, K., Nakagawa, Y. and Humphreys-Beher, M. 1996. Alterations in the secretory response of NOD mice to muscarinic receptor stimulation. Clin. Immunol. Immunopathol. 78:245–255.CrossRefPubMedGoogle Scholar
  23. 23.
    Robinson, C.P., Yamamoto, H., Pech, A.B. and Humphreys-Beher M.G. 1996. Genetically programmed development of salivary gland abnormalities in the NOD (non-obese diabetic)-scid mouse in absence of detectable lymphocitic infiltration: a potential trigger for sialoadenitis of NOD mice. Clin. Immunopathol. 79:50–59.CrossRefGoogle Scholar
  24. 24.
    MacDonald, R.J., Swift, G.H., Prsybyla, A.E. and Chirgwin, J.M. 1987. Isolation of RNA using guanidium salts. Methods in Enzymology. 152: 219–227.CrossRefPubMedGoogle Scholar
  25. 25.
    Freidman, Z.Y., Lowe, M. and Selinger, Z. 1981. β-adrenergic receptor stimulated peroxidase secretion from rat lacrimal gland. Biochimica et Biophysica Acta 675:40–45.CrossRefGoogle Scholar
  26. 26.
    Bromberg, B.B., Cripps, M.M. and Welch, M. H. 1986. Sympathomimetic protein secretion by young and aged lacrimal gland. Curr. Eye Res. 5(3):217–223.CrossRefPubMedGoogle Scholar
  27. 27.
    Cripps, M.M. and Bennett, D.J. 1990. Peptidergic stimulation and inhibition of lacrimal gland adenylate cyclase. Invest. Ophthamol. Vis. Sci. 31:2145–2150.Google Scholar
  28. 28.
    Meneray, M.A. and Bennett, D.J. 1995. Identification of G proteins in lacrimal gland. Invest. Ophthamol. Vis. Sci. 35:4144–4158.Google Scholar
  29. 29.
    Jahn, R., Padel, U., Porsch, P.H. and Soling H.D. 1982. Adrenocorticotropic hormone and α-melanocyte stimulating hormone induce secretion and protein phosphorylation in the rat lacrimal gland by activation of cAMP-dependent pathway. Eur. J. Biochem. 126:623–629.CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 2002

Authors and Affiliations

  • Michele A. Meneray
    • 1
  • Thomas E. Lallier
    • 2
  1. 1.Departments of PhysiologyLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.Cell Biology and AnatomyLouisiana State University Health Sciences CenterNew OrleansUSA

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