Disease relevance of Apbh

• The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene [1].
• The finding that the majority of lymphocytes in both the lacrimal gland inflammatory lesions and renal vasculitis of MRL/lpr mice expressed L3T4 suggests that these cells may be capable of responding to antigen presentation and that an active immunologic response occurs at these sites [2].
• These mice exhibit several phenotypes: mammary tumors, bilateral hyperplasia of the harderian lacrimal gland, primary bronchio-alveolar lung adenocarcinoma, and splenomegaly [3].
• Female (C57BL/6xA/J)F(1) mice undergoing thymectomy on day 3 after birth (d3tx) developed autoimmune ovarian disease (AOD) and autoimmune disease of the lacrimal gland [4].
• Chronic dry eye syndrome affects over 10 million people in the United States; it is associated with inflammation of the lacrimal gland (LG) and in some cases involves T cell infiltration of the conjunctiva [5].

High impact information on Apbh

• Reactive lymphocytes in lacrimal gland and vasculitic renal lesions of autoimmune MRL/lpr mice express L3T4 [2].
• Bmp7 regulates branching morphogenesis of the lacrimal gland by promoting mesenchymal proliferation and condensation [6].
• The lacrimal gland provides an excellent model with which to study the epithelial-mesenchymal interactions that are crucial to the process of branching morphogenesis [6].
• Expression of FGF10 in the mesenchyme adjacent to the presumptive lacrimal bud and absence of lacrimal gland development in FGF10-null mice strongly suggest that it is an endogenous inducer [7].
• FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development [7].

Chemical compound and disease context of Apbh

• CONCLUSIONS: Androgen deficiency may promote the progression of Sjögren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye [8].
• Cyclosporine therapy was evaluated for its effect on the autoimmune disease, particularly in the eye and lacrimal gland [9].
• Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis [10].
• Tumor necrosis factor inhibitor gene expression suppresses lacrimal gland immunopathology in a rabbit model of autoimmune dacryoadenitis [11].

Biological context of Apbh

• Gene expression differences in the lacrimal gland may contribute to susceptibility to lacrimal gland or ocular surface disease [12].
• We found that vascular endothelia in inflamed areas of lacrimal gland expressed vascular cell adhesion molecule (VCAM)-1 and the peripheral node addressin (PNAd), but not mucosal addressin cell adhesion molecule-1 [13].
• Specifically, a 107-bp enhancer and a 1.1-kb sequence within the 4.6-kb untranslated region upstream of exon 0 are required to mediate Pax6 expression in the lens, cornea, lacrimal gland, conjunctiva, or pancreas, respectively [14].
• It appears that in MRL/lpr mice there is defective extrathymic lymphoid apoptosis, permitting a relatively greater expansion of autoreactive T cells, which subsequently invade the lacrimal gland [15].
• CONCLUSIONS: This study demonstrates that corneal trauma has profound effects on the regulation of gene expression in the lacrimal gland and may provide genetic evidence for a cornea-to-lacrimal gland feedback mechanism in dry eye [16].

Anatomical context of Apbh

• These results demonstrate the effects of lacrimal gland, both directly and indirectly through T cells, on B cell differentiation [17].
• Lacrimal gland-directed B cell responses [17].
• We demonstrate that environmental desiccating stress (DS) elicits T cell-mediated inflammation of the cornea, conjunctiva, and LG, but not other organs in mice [5].
• After d3tx, both male and female NZM2328 mice developed 1) accelerated dsDNA autoantibody response, 2) early onset and severe proliferative GN with massive mesangial immune complexes, and 3) autoimmune disease of the thyroid, lacrimal gland, and salivary gland [18].
• Although it is accepted that IgA plasma cells predominate in the lacrimal gland, the factors leading to this prevalence are not known [17].

Associations of Apbh with chemical compounds

• Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency [8]?
• Acetylcholine release and peroxidase secretion (a protein secreted by the lacrimal gland) were measured using a spectrofluorometric assay [19].
• Cyclosporine therapy was effective in reducing the ocular and lacrimal gland disease [9].
• Testosterone exposure also stimulated an increase in lacrimal gland weight and a rise in tear volumes, relative to those measured in the same mice before treatment [20].
• RESULTS: The results demonstrate that 17beta-estradiol, progesterone, or both hormones together significantly influences the expression of hundreds of genes in the mouse lacrimal gland [21].

Physical interactions of Apbh

• Anion exchange transport in the mouse lacrimal gland acinar cell membrane was studied by measuring the intracellular H+ (pHi) and Cl- (aCli) activities with double-barreled ion-selective microelectrodes [22].

Regulatory relationships of Apbh

• Foxc1 is expressed in both the epithelium of the lacrimal gland and the surrounding mesenchyme [23].
• Ectodysplasin and Edar are expressed in separate epithelial compartments in the developing brain and the lacrimal gland [24].
• FasL mRNA and cell surface protein were expressed in salivary and lacrimal gland epithelial cells from 8 and 18 week old NOD, NOD-scid, and BALB/c mice [25].
• In addition, we show that canonical Wnt signaling is able to modulate the levels of Fgf10 and suppress BMP-induced proliferation in the lacrimal gland [26].
• We previously showed that interleukin-1beta (IL-1beta) protein is up regulated in the lacrimal gland of a murine model of Sjögren's syndrome and that exogenous addition of this cytokine inhibits neurotransmitter release and lacrimal gland protein secretion [27].

Other interactions of Apbh

• This suggested that its role in induction is to stimulate proliferation and, in turn, that FGF10 combines with other factors to provide the instructive signals required for lacrimal gland development [7].
• In loss-of-function analyses, we find that Bmp7-null mice have distinctive reductions in lacrimal gland branch number, and that inhibition of Bmp activity in gland explant cultures has a very similar consequence [6].
• This study demonstrates that Foxc1 mediates the BMP signaling required for lacrimal gland development [23].
• Testosterone administration induced a significant increase in the lacrimal gland content of Bax mRNA, but a striking decrease in the lacrimal tissue level of bcl-2 mRNA in F1 and C3H mice [28].
• BMP-3 was also localized in ducts of submandibular and sublingual salivary glands, acini of the lacrimal gland, Purkinje cells in the cerebellum, nerve fibres of the cerebellum and brain, afferent cells of the dorsal root ganglia, inferior alveolar nerve, and peripheral processes of the vestibulocochlear nerve [29].

Analytical, diagnostic and therapeutic context of Apbh

• Northern blot analysis showed that mRNAs for each of these four ABP subunits were lacrimal-gland-specific [12].
• Furthermore, suppression of IgG and IgM responses occurred after co-culture of lacrimal gland cells with Peyer's patch cells [17].
• In lacrimal gland homogenates, [3H]GPIP2 was metabolized to two compounds which upon anion exchange high performance liquid chromatography eluted at positions indicating that they were [3H]GPIP and [3H]GPIP3 [30].
• A protein factor has been purified from lacrimal gland extracts by a combination of ion exchange and gel-filtration chromatography [31].
• To determine subcellular localization, Y2 sense and antisense RNA probes were hybridized to female mouse lacrimal gland frozen sections [32].

References