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PubMed2006

Mechanisms of Disease: primary Sjögren's syndrome and the type I interferon system.

Sjögren's syndrome is a chronic autoimmune disease of largely unknown etiology and pathogenesis. The salivary and lacrimal glands are the main target organs, and key cells and molecules involved in the autoimmune process have been detected in these glands. Chemokines, expressed by epithelial cells, can attract T cells and dendritic cells that produce proinflammatory cytokines, which stimulate the immune response and induce apoptosis in the acinar and ductal epithelial cells. The autoantigens SSA and SSB are translocated to the apoptotic blebs and trigger infiltrating B cells to produce autoantibodies against SSA and SSB. Germinal-center-like structures can form within glandular lymphocyte foci, facilitating the antigen-driven B-cell activation. Many of the autoimmune mechanisms described above can be induced by type I interferon (IFN), and activation of this system in patients with Sjögren's syndrome has been described. A possible scenario is that an initial viral infection induces type I IFN production in salivary glands with a subsequent activation of the adaptive immune system. Resultant autoantibodies form nucleic-acid-containing immune complexes that can trigger prolonged type I IFN production, leading to a self-perpetuating autoimmune reaction. Several potential therapeutic targets for Sjögren's syndrome exist within the type I IFN system.

Autoantibodies↗
PubMed1983

Branched chain fatty acids in phospholipids of guinea pig Harderian gland.

Fatty acid compositions of phosphatidyl ethanolamine and phosphatidyl choline extracted from the guinea pig Harderian gland were examined by gas chromatography and gas chromatography-mass spectrometry. Oleic acid was the major component of both phospholipids, but a large amount of saturated branched chain fatty acids was found: 34.5% in phosphatidyl ethanolamine, and 42.9% in phosphatidyl choline. On the other hand, linolenic and arachidonic acids were not found in these phospholipids. At the 1-position of phosphatidyl choline and phosphatidyl ethanolamine, 54.3% and 40.9% of fatty acids, respectively, had methyl branches. These methyl branches were located at the even-numbered carbon atoms. Branched chain fatty acids were also found at the 2-position of both lipids: 36.2% in phosphatidyl choline and 31.2% in phosphatidyl ethanolamine. The fatty acids of phosphatidyl ethanolamine and phosphatidyl choline from liver, cerebrum, cerebellum, erythrocytes, and plasma of the same animal were also analyzed. Saturated and unsaturated fatty acids, including arachidonic acid, were the major components. Branched chain fatty acids were also found in these lipids, but in very small amounts.

Animals↗
PubMed1979

Inhibition and facilitation of lacrimal flow by beta-adrenergic drugs.

The effects of adrenergic beta-stimulating and beta-blocking compounds on tear flow were studied in conscious rabbits with a modified Schirmer technique. The tear flow was significantly increased by the unselective beta-adrenergic agonist isoprenaline and by the selective beta1-agonist H 80/62 (racemic Prenalterol, Hässle, Sweden). The effects of the agonists were blocked by the unselective beta-adrenergic antagonist propranolol (Inderal) and by the selective beta1-antagonist metoprolol (Seloken, Lopressor). The experimental data favoured the hypothesis that the beta-receptors involved in the regulation of the tear flow were of the beta1-type. The anatomical location of these beta-receptors is at present unclear but in vitro experiments performed on the rabbit lacrimal glands indicated that the receptors were probably not located on cholinergic nerve-endings as the release of acetylcholine was not influenced by isoprenaline.

Acetylcholine↗
PubMed1990

Age- and gender-related influence on the lacrimal gland and tears.

Previous research has demonstrated that distinct, gender-related differences exist in lacrimal glands in a variety of adult species. The objective of the current investigation was to examine whether this influence of gender extends throughout development and aging. Towards that end, morphological parameters of the lacrimal gland, as well as the volume, protein and IgG content of tears, were measured in male and female infant, preweanling, pubertal, adult, mid-life and senescent rats. Our results showed that dramatic, age-related variations occurred in the weight and morphological appearance of the lacrimal gland. Moreover, the magnitude of structural changes was dependent upon gender. Acinar area was significantly greater in lacrimal tissue of males, as compared to females, at all ages except pre-weanling; this sexual dimorphism was most evident in senescent rats. In contrast, acinar density in lacrimal glands of females was higher than, or equal to, that of males throughout development and aging. With regard to tears, pronounced increases were evident in tear volume, protein and IgG content from the pre-weanling stage to adulthood. After this time, these tear indices tended either to plateau or rise slightly until senescence. Gender had little or no impact of the volume of, or protein and IgG level in, tears. Of interest, the IgG/protein ratio in tears was 49- to 105-fold less than that found in lacrimal tissue, indicating that IgG moves down a gradient from the lacrimal gland to tears. Overall, our findings demonstrate that gender has a significant influence on lacrimal gland structure during development and aging. However, this impact is limited with respect to tear volume and protein content.

Aging↗
PubMed1970

Harderian gland: development and influence of early hormonal treatment on porphyrin content.

The porphyrin content of the rat Harderian gland remains low until 12 days of age at which time both porphyrin content and concentration rapidly increase. Intraperitoneal administration of tetraiodothyronine (thyroxine) into newborn animals advances the appearance of porphyrin in the gland. Conversely, a single injection of cortisol acetate into newborns retards the appearance of porphyrin. The time of porphyrin appearance in the gland parallels the time for maturation of the evoked cortical response to visual stimulation in normal and hormone-treated animals.

Age Factors↗
PubMed1975

The effects of hypophysectomy and of bovine growth hormone on the responses to testosterone of prostate, preputial, Harderian and lachrymal glands and of brown adipose tissue in the rat.

The relative responses to testosterone of the prostate, preputial, Harderian, and lachrymal glands, the seminal vesicles and the brown adipose tissue, have been compared in litter-mate, castrated and hypophysectomized-castrated rats, with or without treatment with bovine GH. The responses of both prostate and preputial glands, though not the seminal vesicles, were reduced by hypophysectomy, and restored by GH. Growth hormone had some independent action on the preputial glands, but most of its effect was synergistic with testosterone. The respinse of brown adipose tissue to testosterone was similarly reduced by hypophysectomy, but was not restored by the GH. The weights of the Harderian and lachrymal glands were not affected by castration, but they were considerably reduced by hypophysectomy. Growth hormone had a slight restorative effect on the Harderian glands, but none on the lachrymal glands.

Adipose Tissue, Brown↗
PubMed2005

Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological and pathological findings as well as the salivary gland dysfunction of Sjogren's syndrome.

Sjögren's syndrome is a poorly understood autoimmune inflammatory illness that affects the salivary and lacrimal glands as well as other organ systems. We undertook the present study to determine whether mice immunized with short peptides from the 60-kDa Ro (or SSA) Ag, which is a common target of the autoimmunity of Sjögren's syndrome, develop an illness similar to Sjögren's syndrome. BALB/c mice were immunized with one of two short peptides from 60-kDa Ro that are know to induce epitope spreading. The animals were analyzed for the presence of anti-Ro and anti-La (or SSB) in the sera by immunoblot and ELISA. Salivary glands were collected and examined by histology after H&E staining. Salivary lymphocytes were purified and studied for cell surface makers by fluorescence-activated cell sorting. Timed stimulated salivary flow was measured. As reported previously, BALB/c mice immunized with 60-kDa Ro peptides developed an immune response directed against the entire Ro/La ribonucleoprotein particle that was similar to that found in humans with lupus or Sjögren's syndrome. Functional studies showed a statistical decrease in salivary flow in immunized mice compared with controls. Furthermore, there were lymphocytic infiltrates in the salivary glands of immunized animals that were not present in controls. The infiltrates consisted of both CD4- and CD8+ T lymphocytes as well as B lymphocytes. BALB/c mice immunized with 60-kDa Ro peptides develop anti-Ro, salivary gland lymphocyte infiltrates, and salivary dysfunction that is highly reminiscent of human Sjögren's syndrome.

Animals↗
PubMed1978

Effect of hypervitaminosis A on the Harderian gland in rats. A morphologic and morphometric study.

Daily administration of 100 I.U. vitamin A/gram body weight to rats, for a period of 15 days, had the following effects: Body weight of rats treated with excess vitamin A was lower (84.0 g) than that of the controls (147.0 g). The weight of the Harderian gland was lower of rats injected with vitamin A (54.0 mg) than for the controls (87.0 mg). Histological examination of the Harderian gland in the hypervitaminotic animal showed smaller acini, lower cells, wide lumina and small nuclei when compared with the controls. These data were confirmed with morphometric techniques.

Animals↗
PubMed1982

Effect of quercetin on the course of mengo virus infection in immunodeficient and normal mice. A histologic study.

Quercetin protects mice from lethal Mengo M virus infection when given orally 12 and 1 hr before and 8, 24, 36, 48 and 56 hr after inoculation. No differences in the course of infection have been found between normal splenectomized or congenitally athymic mice. Likewise the effect of drug treatment was similar in all three models. Necrotic lesions in the main target organs (central nervous system, salivary and lacrimal glands, thymus, pancreas, kidneys and spleen) from both normal and immunodeficient animals were less severe and developed later in quercetin-treated mice than in placebo-treated ones. In a few quercetin-treated virus-infected survivors a slight and persistent encephalitis was seen. Quercetin enhanced the graft-versus-host reaction, but failed to affect the humoral antibody response of mice to sheep red blood cells. It is concluded that T- and B-lymphocytes seem involved neither in the pathogenesis of acute Mengo virus infection nor in the antiviral effect of quercetin.

Animals↗
PubMed2003

[Eye-associated lymphoid tissue (EALT) is continuously spread throughout the ocular surface from the lacrimal gland to the lacrimal drainage system].

INTRODUCTION: Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear. MATERIAL AND METHODS: Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy. RESULTS: A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye. CONCLUSION: These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.

Aged↗
PubMed2006

A novel mouse protein differentially regulated by androgens in the submandibular and lacrimal glands.

We characterized a cDNA clone derived from the female mouse submandibular gland (SMG). The transcript of this cDNA was approximately 1.2kb in size and predicted to code a 165-amino acid protein with a putative signal peptide for a secretory pathway. This protein, named submandibular androgen-repressed protein (SMARP), had homology in the N-terminal region with members of the glutamine/glutamic acid-rich protein (GRP) family from rats. Northern blot analysis revealed that SMARP mRNA is expressed, out of the major mouse organs, only in the SMG and exorbital lacrimal gland (LG), with much more abundance in the former. For the SMG, the level of SMARP mRNA was 36 times higher in females than males, whereas for the LG it was 28 times higher in males than females. Furthermore, the level of SMARP mRNA was increased in the SMG but reduced in the LG with castration in males, whereas it was reduced in SMG but increased in LG after administration of testosterone in females or castrated males. In situ hybridization detected the signal for SMARP mRNA in the female SMG, and immunohistochemistry detected the signal for SMARP protein in the female SMG and male LG. In the female SMG, SMARP mRNA, and protein were localized intensively in a subpopulation of acinar cells, whereas in the male LG, SMARP protein was distributed diffusely in all acinar cells. These results suggested that SMARP is a secretory protein whose expression is regulated by androgens negatively in the SMG and positively in the LG.

Androgens↗
PubMedDate not supplied

Dacryoliths in a series of dacryocystorhinostomies: histologic and chemical analysis.

PURPOSE: To present the clinical and intraoperative characteristics of dacryolith cases, to present their histologic and chemical analysis, and to relate the findings with the probable causes of their formation in a series of dacryocystorhinostomies performed in northern Greece. METHODS: In a series of 242 dacryocystorhinostomies in patients with chronic dacryocystitis, dacryoliths large enough to perform an accurate chemical analysis and a light histologic examination were found in five cases. The chemical analysis was based on atomic absorption spectrophotometry and atomic emission spectrometry. RESULTS: These five cases concerned relatively young patients who presented symptoms of short duration as compared to the other dacryocystorhinostomy cases. In three of them, irregularities of the lacrimal sac wall were observed. The final postoperative results were satisfactory. The histologic examination revealed acellular amorphous organic material and limited areas with characteristics of calcium salt depositions. The chemical analysis showed mainly organic and minimal inorganic material. CONCLUSIONS: The irregularities of the lacrimal sac wall and the consequent flow disorders within the sac and the histologic and chemical analysis of the dacryoliths provide evidence for etiologic consideration.

Adult↗