Adamts18 Deficiency Causes Spontaneous SMG Fibrogenesis in Adult Mice

2021 ◽  
pp. 002203452110292
Author(s):  
N. Yang ◽  
Q. Zhang ◽  
S. Ye ◽  
T. Lu ◽  
M. Sun ◽  
...  
Keyword(s):  
Submandibular Gland ◽  
Plasma Cells ◽  
Lymphocytic Infiltration ◽  
Branching Morphogenesis ◽  
Submandibular Salivary Gland ◽  
Autoimmune Reaction ◽  
Chronic Sclerosing Sialadenitis ◽  
Adult Mice ◽  
Extracellular Proteinases ◽  
Monocytes And Macrophages

Chronic sclerosing sialadenitis of the submandibular gland (also known as Küttner tumor) is characterized by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis. The pathogenesis of this disease has been unclear, but it is associated with immune disorders. ADAMTS18 is a member of the ADAMTS superfamily of extracellular proteinases. In this study, we showed that Adamts18 is highly expressed in submandibular salivary gland (SMG) during embryonic development and decreases but is retained in adult SMG tissue in mice. Adamts18 deficiency led to reduced cleft formation and epithelial branching in embryonic SMG before embryonic day 15.5 in mice. No significant histologic changes in the later stages of branching or the morphology of SMG were detected in Adamts18−/− mice. However, Adamts18 deficiency causes spontaneous SMG fibrogenesis and fibrosis in adult mice. At 8 wk of age, Adamts18−/− mice began to manifest the first signs of pathologic changes of mild fibrosis and CD11b+ cell infiltration in SMG tissues. At ≥8 mo, all male and female Adamts18−/− mice developed unilateral or bilateral SMG scleroma that is similar to patients with chronic sclerosing sialadenitis of the submandibular gland. Adamts18−/− mice also showed secretory dysfunction and severe dental caries. Histologically, SMG scleroma is characterized by progressive periductal fibrosis, acinar atrophy, irregular duct ectasis, and dense infiltration of IgG-positive plasma cells. A significant infiltration of CD4+ T lymphocytes and CD11b+ monocytes and macrophages was also detected in the SMG scleroma of Adamts18−/− mice. The levels of TGF-β1, IL-6, and IL-33 were significantly increased in Adamts18−/− SMGs, which induces chronic inflammation and myofibroblast activation, ultimately leading to fibrosis. This study indicates that Adamts18 regulates the early branching morphogenesis of embryonic SMG and plays a role in protecting from spontaneous SMG fibrogenesis via modulating local inflammation, autoimmune reaction, and myofibroblast activation in adult mice.

scholarly journals Thoracic Paravertebral Mass as an Infrequent Manifestation of IgG4-Related Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Melissa Matzumura Kuan ◽  
Bernard Rubin ◽  
Alireza Meysami
Keyword(s):  
Submandibular Gland ◽  
Plasma Cells ◽  
Inflammatory Cells ◽  
Disease Recurrence ◽  
Tissue Mass ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Chronic Sclerosing Sialadenitis ◽  
Resistant Disease ◽  
Paravertebral Mass

Case. A 50-year-old African American male presented with abdominal pain and significant weight loss. On physical examination, he had parotid and submandibular gland enlargement associated with right eye proptosis. Computed tomography showed a thoracic paravertebral soft tissue mass, enlarged lymph nodes, and ascending aortic aneurysm. Laboratory results were remarkable for elevated total IgG and IgG4 subclass. The submandibular gland pathology revealed chronic sclerosing sialadenitis, with a large subset of inflammatory cells positively staining for IgG4. The histology of the paravertebral mass demonstrated fibrosclerosis with increased lymphocytic infiltrate, associated with increased IgG4 plasma cells. He was diagnosed with immunoglobulin G4-related disease (IgG4-RD). Steroid therapy initially yielded improvement; however, after steroids were stopped, there was disease recurrence. Prednisone was restarted, and the plan was to start him on rituximab. Interestingly, the patient’s brother also had IgG4-RD. Conclusion. IgG4-RD can present as a paravertebral mass which is usually responsive to steroids; however, recurrent and resistant disease can be seen for which steroid-sparing agents such as rituximab should be considered. In addition, to the best of our knowledge, this is the first reported case of IgG4-RD in two family members presenting as a paravertebral mass, highlighting an exciting area for more research in the future.

Extra-nodal Rosai-Dorfman Disease Confined to Breast

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S41-S42
Author(s):  
E Ozluk ◽  
R Shackelford
Keyword(s):  
Plasma Cells ◽  
African American Woman ◽  
American Woman ◽  
Lymphocytic Infiltration ◽  
Needle Aspiration ◽  
Left Breast ◽  
Unknown Etiology ◽  
Diagnostic Challenge ◽  
Ductal Cells ◽  
Rosai Dorfman Disease

Abstract Introduction/Objective First described by Rosai and Dorfman in 1969, Rosai-Dorfman Disease (RDD) is an uncommon, idiopathic, reactive lymph node process with an unknown etiology. It may involve extra-nodal organs including the skin, bone, soft tissue, and eyes. However, breast involvement is rare and RDD confined to breast without nodal involvement is extremely uncommon. Methods Here we present a case of RDD confined to breast. The patient was a 51-year-old African American woman who was found to have an irregular, solid left breast mass on routine mammogram, which had speculated irregular margins and measured of 37.0 x 32.0 x 32.0 mm. She did not have any symptoms, nor any palpable lymph nodes. The clinician stated that the lesion was highly suspicious for a breast malignancy and requested a fine needle aspiration (FNA) of the mass, followed by total excision. Results An FNA was interpreted as atypical histiocytic cells in a mixed lymphoid background. Histopathologic examination revealed an ill-defined mass with sheets of histiocytes, plasma cells, and a mixed lymphocytic population, with occasional germinal centers. Some of the histiocytes were spindle shaped and associated with storiform collagen deposition. The histiocytes had single and multiple nuclei and exhibited occasional emperipolesis. Immunohistochemical staining with S100 diffusely highlighted the histiocytes, whereas CD1a was negative. CD3 and CD20 immunostains were positive for mixed-type lymphocytic infiltration. Cytokeratin staining was performed and reassuringly stained only the benign ductal cells. A diagnosis of RDD of the breast was made, based on these histopathologic findings. Conclusion We report an example of an extra-nodal RDD involving the mammary gland that was initially suspected to be breast carcinoma. RDD may still be a diagnostic challenge, especially in a patient with suspected carcinoma. It is the pathologist’s role to lead the clinician to the proper diagnosis and render a correct histopathologic diagnosis.

scholarly journals The effect of low LET (Linear Energy Transfer) ionizing radiation to catalase activity of wistar’s submandibular gland

2016 ◽  
Vol 1 (3) ◽  
pp. 145
Author(s):  
Nevy T. Putri ◽  
Sarianoferni Sarianoferni ◽  
Endah Wahjuningsih
Keyword(s):  
Energy Transfer ◽  
Ionizing Radiation ◽  
Submandibular Gland ◽  
Rattus Norvegicus ◽  
Catalase Activity ◽  
Linear Energy Transfer ◽  
Submandibular Salivary Gland ◽  
X Rays ◽  
X Ray ◽  
Bonferroni Test

Intraoral periapical radiograph examination is the additional examination which is the most widely used in Dentistry. This radiograph examination using an x-ray ionizing radiation with low LET (Linear Energy Transfer), and may affect submandibular salivary gland. Ionizing radiation exposure can cause damage by inducing a series of changes at the molecular and cellular level. This study aimed to prove the effects of x-ray ionizing radiation with low LET towards the catalase activity of Rattus norvegicus strain Wistar’s submandibular gland. The subjects were 28 male Wistar rats and divided into 4 groups (n=7). Three groups were exposed 4, 8 and 14 times to radiation with 0.002 µSv for each exposure. The catalase activity of each rat was examined by a spectrophotometer. Data were analyzed using one-way ANOVA followed by Bonferroni test. The results showed the average of catalase activity on Wistar rat’s submandibular gland, respectively for: 0.150±0.0895 (KK), 0.1405±0.0607 (K1), 0.1228±0.0290 (K2), 0.1227±0.0556 (K3). Data showed significant differences of catalase activity between test groups, but showed not significant differences of catalase activity between each groups of Rattus norvegicus strain Wistar’s submandibular gland. In this study concluded decreased catalase activity of Rattus norvegicus strain Wistar’s submandibular gland resulting from x-rays ionizing radiation by 4 times, 8 times and 14 times exposures.

Pathology

2020 ◽  
pp. 16-24
Keyword(s):  
T Cells ◽  
Hashimoto’S Thyroiditis ◽  
Plasma Cells ◽  
Lymphocytic Infiltration ◽  
Lymphoid Cells ◽  
Hashimoto's Thyroiditis ◽  
Gamma Delta T Cells ◽  
Cellular Infiltration ◽  
Pyramidal Lobe ◽  
Grade Iii

Grossly, thyroid enlargement in Hashimoto's thyroiditis (HT) is generally symmetrical, often with a characteristic conspicuous pyramidal lobe. The tissue involved by HT is pinkish-tan to frankly yellowish in color and tends to have a rubbery firmness. There is no necrosis or calcification. The capsule is intact and non-adherent to peri-thyroid structures. Microscopically, there is a diffuse process consisting of a combination of epithelial cell destruction, lymphoid cellular infiltration, and fibrosis. Lymphocytes are predominantly T-cells and plasma cells. Most infiltrating T-cells have α/β T-cell receptors. Gamma/delta T-cells are rare. Hashimoto's thyroiditis has been graded based on lymphocytic infiltration seen on cytology, into Grades 0-III, where Grade 0 means no lymphoid cells and Grade III severe lymphoid cell infiltration. Deposits of dense material representing IgG are found along the basement membrane on electron microscopy. This chapter explores the pathology of Hashimoto's disease.

scholarly journals Protective Immunity to Rotavirus Shedding in the Absence of Interleukin-6: Th1 Cells and Immunoglobulin A Develop Normally

2000 ◽  
Vol 74 (11) ◽  
pp. 5250-5256 ◽  
Author(s):  
John L. VanCott ◽  
Manuel A. Franco ◽  
Harry B. Greenberg ◽  
Steffanie Sabbaj ◽  
Baozhing Tang ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Protective Immunity ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Specific Response ◽  
T Helper 1 ◽  
Adult Mice ◽  
Iga Response ◽  
Antigen Presenting ◽  
Interferon Responses

ABSTRACT We investigated whether interleukin-6 (IL-6) was required for the development of immunoglobulin A (IgA)- and T-helper 1 (Th1)-associated protective immune responses to rotavirus by using adult IL-6-deficient mice [BALB/c and (C57BL/6 × O1a)F2 backgrounds]. Naive IL-6− mice had normal frequencies of IgA plasma cells in the gastrointestinal tract. Consistent with this, total levels of IgA in fecal extracts, saliva, and sera were unaltered. In specific response to oral infection with rhesus rotavirus, IL-6−and IL-6+ mice exhibited efficient Th1-type gamma interferon responses in Peyer's patches with high levels of serum IgG2a and intestinal IgA. Although there was an increase in Th2-type IL-4 in CD4+ T cells from IL-6− mice following restimulation with rotavirus antigen in the presence of irradiated antigen-presenting cells, unfractionated Peyer's patch cells failed to produce a significant increase in IL-4. Moreover, virus-specific IgG1 in serum was not significantly increased in IL-6− mice in comparison with IL-6+ mice. Following oral inoculation with murine rotavirus, IL-6− and IL-6+ mice mediated clearance of rotavirus and mounted a strong IgA response. When IL-6− and IL-6+ mice [(C57BL/6 × O1a)F2 background] were orally inoculated with rhesus rotavirus and later challenged with murine rotavirus, all of the mice maintained high levels of IgA in feces and were protected against reinfection. Thus, IL-6 failed to provide unique functions in the development of IgA-secreting B cells and in the establishment of Th1-associated protective immunity against rotavirus infection in adult mice.

scholarly journals Chronic Sclerosing Sialadenitis of the Submandibular Gland is Mainly Due to a T Lymphocyte Immune Reaction

2002 ◽  
Vol 15 (8) ◽  
pp. 845-852 ◽  
Author(s):  
Markus Tiemann ◽  
Afshin Teymoortash ◽  
Carsten Schrader ◽  
Jochen A. Werner ◽  
Reza Parwaresch ◽  
...  
Keyword(s):  
Submandibular Gland ◽  
T Lymphocyte ◽  
Immune Reaction ◽  
Chronic Sclerosing Sialadenitis

scholarly journals Complementary Signaling through flt3 and Interleukin-7 Receptor α Is Indispensable for Fetal and Adult B Cell Genesis

2003 ◽  
Vol 198 (10) ◽  
pp. 1495-1506 ◽  
Author(s):  
Ewa Sitnicka ◽  
Cord Brakebusch ◽  
Inga-Lill Martensson ◽  
Marcus Svensson ◽  
William W. Agace ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Target Genes ◽  
Plasma Cells ◽  
Tyrosine Kinase Receptor ◽  
Gamma Chain ◽  
Interleukin 7 ◽  
Adult Mice ◽  
Cell Genesis ◽  
Cell Commitment

Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7Rα, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7Rα and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL−/− × IL-7Rα−/− BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7Rα−/− mice, FL−/− × IL-7Rα−/− mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7Rα are indispensable for fetal and adult B cell development.

Sialolithiasis in a residual Wharton's duct after excision of a submandibular salivary gland

2006 ◽  
Vol 121 (2) ◽  
pp. 182-185 ◽  
Author(s):  
M R Markiewicz ◽  
J E Margarone 3rd ◽  
J L Tapia ◽  
A Aguirre
Keyword(s):  
Salivary Gland ◽  
Submandibular Gland ◽  
Acute Infection ◽  
Surgical Techniques ◽  
Surgical Approaches ◽  
Submandibular Salivary Gland ◽  
Major Salivary Gland ◽  
Continuous Growth ◽  
Wharton’S Duct ◽  
Submandibular Gland Excision

Treatment of salivary stones includes both surgical and non-surgical techniques. Surgical approaches range from excision of the sialolith, for those near the duct orifice, to removal of the affected salivary gland and its associated duct, for stones near the hilum of the gland. We present a case of two sialoliths triggering an acute infection in a residual Wharton's duct, 12 years after the removal of the associated submandibular gland. Excision of the sialoliths and treatment of the infected duct via sialodochoplasty was successfully performed in this patient. If the Wharton's duct is not removed with the associated submandibular gland, the potential for infection and continuous growth of dormant calcifications exists. We also address the aetiology, pathogenesis, and management of patients with sialolithiasis in the absence of a major salivary gland.

Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse

1985 ◽  
Vol 63 (9) ◽  
pp. 1151-1154
Author(s):  
Peter Walker
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Epidermal Growth Factor ◽  
Thyroid Hormones ◽  
Submandibular Gland ◽  
Adult Mice ◽  
Neonatal Hyperthyroidism ◽  
Epidermal Growth ◽  
And Control

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 μg of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay. SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P < 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P < 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 μg/d) of adult mice, SMG weight in NH mice increased significantly (P < 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P < 0.01). However, the magnitude of the increase was markedly obtunded in adult NH mice. These observations indicate that thyroid hormones precociously and exponentially increase SMG EGF content and concentration in neonatal mice. The marked increases strongly suggest thyroid hormone mediated synthesis of EGF and acceleration of maturation of gene expression for EGF synthesis. In addition, NH appears to modify thyroid hormone regulation of gene expression for EGF synthesis in adult mice.

Sign in / Sign up

Export Citation Format

Share Document