Ultrastructure of myoepithelial cells as a target cell in sialoadenitis of submandibular glands of lupus-prone female NZBxNZWF1 mice.
ABSTRACT The changes of myoepithelial cells of sialoadenitis in submandibular glands in lupus-prone female NZB x NZWF1 (B/WF1) mice, a model for human secondary Sjögren's syndrome (sSS), were examined ultrastructurally. Inflammatory foci consisting of mainly lymphoid cells (lymphocytes and plasma cells) in the interlobular interstitium began to develop from 18 weeks of ages, and those were found within acini from the age of 25 weeks. These were paralleled with the production of anti-double-stranded deoxyribonucleic acid and anti-Ro/SS-A antibodies with age. Infiltrated lymphoid cells consisted of CD4+ T cells and Ig+ (or IgG2a+) cells. Electron microscopy revealed destruction of myoepithelial cells with lysis of basement membranes contacted with either lymphocytes or plasma cells. These led to the destruction (degeneration and necrosis) of the epithelium in striated and intercalated ducts and acinar epithelium. Further destruction of those cells occurred by the invasion of lymphocytes into the epithelial layers. Small numbers of apoptotic myoepithelium and duct epithelium from the age of 25 to 36 weeks and an increase of those cells in survived mice at 44 weeks of age were observed. The present study suggests that the myoepithelium may be one of the target cells and that the destruction of myoepithelial cells by infiltrated lymphoid cells may precede the destruction of acinar ducts and epithelium in sialoadenitis in sSS.
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ABSTRACT: The present study has examined relationship between cutaneous microvessel injury and adhesion molecule expression on the endothelium by cytokines in NZBxNZWF1 (B/WF1) mice, a model for human systemic lupus erythematosus. In advanced ages associated with overt clinical manifestation, but not in early ages, neutrophils with a minor proportion of monocytes and lymphocytes mainly adhered to the endothelium of capillary and the venule with fragmentation (leukocytoclasis), leading to the vascular injury (leukocytoclastic vasculitis). This was confirmed by the leak of monstral blue from the blood vessel. At this stage LFA-1+ leukocytes adhered to intensely expressed ICAM-1 on the endothelium, and this was paralleled with a significant rise in IL-1 alpha and TNF-alpha in the circulation. The present study suggests that IL-1 alpha and TNF-alpha may, at least in part, be responsible for the increased ICAM-1 expression on endothelium in cutaneous microvessels, resulting in the vascular injury characterized by neutrophilic leukocytoclasis in B/WF1 mice.Histology and histopathology 02/2005; 20(1):45-52. · 2.28 Impact Factor
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ABSTRACT: This study was designed to investigate the relationship between cellular infiltration and periductal laminin expression of the submandibular salivary gland in female autoimmune NZBxNZWF(1) mice, which are used as an animal model for secondary human Sjögren's syndrome. In NZBxNZWF(1) mice, but not in non-autoimmune control (BALB/c) mice, early submandibular salivary gland lesions were characterized by infiltration of mononuclear cells around vessels and ducts in the interstitial tissues, increasing with age. Destruction and hyperplasia of ductal epithelial cells occurred, with extensive local infiltration of mononuclear cells. Laminin expression around the ducts was significantly higher in young NZBxNZWF(1) mice than that in control (BALB/c and DBA/1) mice. Periductal laminin expression increased in NZBxNZWF(1)mice with age. In addition VLA-6, which is a ligand for laminin, was expressed by the infiltrating cells. These results suggest that laminin expression is associated with the cellular infiltration of the submandibular salivary gland of NZBxNZWF(1) mice.Journal of Comparative Pathology 08/2001; 125(2-3):110-6. · 1.38 Impact Factor
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ABSTRACT: The expression 'autoimmune epithelitis' has been proposed as an alternative for Sjögren's syndrome (SS) based on data pointing out the central role of the epithelial cell in the pathogenesis of the syndrome. Clinically, apart from exocrine glands that are the main target, the epithelial component of the other organs such as kidneys, liver, lungs or thyroid is commonly affected resulting in various extraglandular manifestations. On the other hand, at the molecular and cellular level, the epithelial cell plays a major role in the initiation and perpetuation of the autoimmune lesion. Mechanisms such as antigen presentation, apoptosis, chemokine production or germinal center formation lie in the center of SS pathogenesis and the epithelial cell has a very important role. Herein, we present both aspects, review the data that support the proposed terminology and finally, suggest a unifying theory for the pathogenesis of SS.Oral Diseases 12/2006; 12(6):523-32. · 2.38 Impact Factor