Peptide‐containing nerves in labial salivary glands in sjögren's syndrome

Abstract

Objective. The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sjogren's syndrome patients were compared with those in salivary glands from 7 healthy controls.Methods. Results. Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas.Conclusion. This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.Aside from Sjogren's syndrome, an autoimmune disease of unknown etiology characterized by keratoconjunctivitis sicca, xerostomia, and focal adenitis, psychogenic and iatrogenic factors are also common causes of "dry mouth." These factors relate, respectively, to inhibitory influences of higher central nervous system control on salivary nuclei and to peripheral anticholinergic effects, and thus illustrate the role of the autonomic nervous system in the control of reflex salivary flow. The sialopenia of Sjogren's syndrome, however, has been generally attributed to autoimmune destruction of the glandular parenchyma, the flow of saliva being roughly proportional to the mass of the secretory end-piece elements. More recently, it has become evident that in addition to the integrated vascular, motor, and secretory control of reflex salivary flow, the autonomic nervous system delivers trophic stimuli to parenchymal tissue ( 1 4 ) .

Salivary VIP concentrations are elevated in humans after acute stress

“…A possibility is the relative distribution of the peptides in salivary glands. For example, Konttinen found in labial salivary glands the Acini, intralobular ducts, small arteries and post capillary veins were richly innervated by VIP-IR fibers whereas NPY-IR was restricted to blood vessels (Konttinen et al, 1992). This difference in distribution could account for the difference in salivary VIP-IR and salivary NPY-IR that we have observed in this study.…”

“…And specifically, both NPY and VIP have been detected in the autonomic nerve fibers of human labial salivary glands (Konttinen et al, 1992;Feher et al, 1999).…”

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome

“…A decrease in neural innervation; this response, which may occur in areas of extensive inflammation, has been observed in salivary glands of pSS and sSS patients [103, 104]…”

Transfer of human serum IgG to nonobese diabetic Igμ null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren’s syndrome

“…Our previous studies in NOD mice have shown decreased receptor density and intracellular signal transduction components, along with autoantibody populations directed against the ␤-adrenergic and muscarinic͞ cholinergic receptors (17,18). Alterations also have been detected in the glandular innervation of the exocrine tissues from Sjögren's syndrome patients (30,31). Recent analyses of autoantibodies from primary Sjögren's syndrome patients have detected antimuscarinic receptor activity capable of acting as a neural receptor agonist (19,32,33).…”