Rheumatology 2000; 39: 1226-1233
© 2000 British Society for Rheumatology
An investigation of interactions between the immune system and stimulus–secretion coupling in mouse submandibular acinar cells. A possible mechanism to account for reduced salivary flow rates associated with the onset of Sjögren's syndrome
Department of Clinical Dental Sciences, The University of Liverpool, Liverpool and
1 Department of Immunology, The University of Liverpool, Liverpool, UK
Objectives. To determine whether chronic exposure to lymphocyte-derived cytokines could inhibit the fluid secretory mechanism in salivary gland acinar cells and so account for the loss of gland function seen in the early stages of Sjögren's syndrome.
Methods. Mouse submandibular acinar cells maintained in primary culture were exposed to a profile of cytokines produced by concanavalin A-activated splenic lymphocytes in vitro for periods up to 72 h. Agonist-evoked changes in intracellular Ca2+ were determined microfluorimetrically in both control and cytokine-treated cells.
Results. Acinar cells maintained in primary culture in the presence of cytokines for up to 72 h were able to mobilize intracellular calcium in response to stimulus by acetylcholine in an identical fashion to those maintained in primary culture in the absence of cytokines. Acute application of the conditioned medium produced by the activated lymphocytes had an antisecretory effect on acetylcholine-evoked Ca2+ mobilization, which was found to be mediated by cholinesterase rather than by cytokines.
Conclusion. Neither chronic nor acute exposure to the profile of cytokines released by concanavalin A-activated splenic lymphocytes interfered in any way with the second messenger cascade and fluid and electrolyte secretion in acinar cells. Our data suggest an alternative hypothesis, in which elevated levels of cholinesterase can metabolize acetylcholine released within the salivary glands and thus prevent fluid secretion.
KEY WORDS: Sjögren's syndrome, Cytokines, Cholinesterase, Intracellular calcium, Signal transduction.
Correspondence to: P. M. Smith, Department of Clinical Dental Sciences, The University of Liverpool, Edwards Building, Daulby Street, Liverpool L69 3GN, UK.
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