scholarly journals Pathogenesis of Anti–PIT-1 Antibody Syndrome: PIT-1 Presentation by HLA Class I on Anterior Pituitary Cells

2019 ◽  
Vol 3 (11) ◽  
pp. 1969-1978 ◽  
Author(s):  
Keitaro Kanie ◽  
Hironori Bando ◽  
Genzo Iguchi ◽  
Keiko Muguruma ◽  
Ryusaku Matsumoto ◽  
...  
Keyword(s):  
Cell Surface ◽  
Anterior Pituitary ◽  
Hla Class I ◽  
Class I ◽  
Gh3 Cells ◽  
Proximity Ligation Assay ◽  
Pituitary Cells ◽  
Anterior Pituitary Cells ◽  
Hla Class I Molecules ◽  
Presentation Pathway

Abstract Context Anti–pituitary-specific transcriptional factor-1 (anti–PIT-1) antibody syndrome is characterized by acquired and specific deficiencies in growth hormone, prolactin, and thyroid-stimulating hormone. Although PIT-1–reactive cytotoxic T lymphocytes (CTLs) have been speculated to recognize anterior pituitary cells and to cause the injury in the pathogenesis of the syndrome, it remains unclear whether endogenous PIT-1 protein is processed through the proteolytic pathway and presented as an antigen on anterior pituitary cells. Objective To examine how PIT-1 protein is processed and whether its epitope is presented by major histocompatibility complex (MHC)/HLA class I on anterior pituitary cells. Materials and Methods Immunofluorescence staining and proximity ligation assay (PLA) were performed using anti–PIT-1 antibody and patients’ sera on PIT-1–expressing cell line GH3 cells and human induced pluripotent stem cell (iPSC)-derived pituitary tissues. Results PIT-1 was colocalized with MHC class I molecules, calnexin, and GM130 in the cytosol. PLA results showed that PIT-1 epitope was presented by MHC/HLA class I molecules on the cell surface of GH3 cells and iPSC-derived pituitary cells. The number of PIT-1/HLA complexes on the cell surface of pituitary cells in the patient was comparable with that in the control subject. Conclusions Our data indicate that PIT-1 protein is processed in the antigen presentation pathway and that its epitopes are presented by in MHC/HLA class I on anterior pituitary cells, supporting the hypothesis that PIT-1–reactive CTLs caused the cell-specific damage. It is also suggested that number of epitope presentation was not associated with the pathogenesis of anti–PIT-1 antibody syndrome.

scholarly journals Spontaneous and Receptor-Controlled Soluble Guanylyl Cyclase Activity in Anterior Pituitary Cells

2001 ◽  
Vol 15 (6) ◽  
pp. 1010-1022 ◽  
Author(s):  
Tatjana S. Kostic ◽  
Silvana A. Andric ◽  
Stanko S. Stojilkovic
Keyword(s):  
Adenylyl Cyclase ◽  
Guanylyl Cyclase ◽  
Anterior Pituitary ◽  
Soluble Guanylyl Cyclase ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Cgmp Production ◽  
Pituitary Tissue ◽  
Anterior Pituitary Cells ◽  
Inducible Nos

Abstract Nitric oxide (NO)-dependent soluble guanylyl cyclase (sGC) is operative in mammalian cells, but its presence and the role in cGMP production in pituitary cells have been incompletely characterized. Here we show that sGC is expressed in pituitary tissue and dispersed cells, enriched lactotrophs and somatotrophs, and GH3 immortalized cells, and that this enzyme is exclusively responsible for cGMP production in unstimulated cells. Basal sGC activity was partially dependent on voltage-gated calcium influx, and both calcium-sensitive NO synthases (NOS), neuronal and endothelial, were expressed in pituitary tissue and mixed cells, enriched lactotrophs and somatotrophs, and GH3 cells. Calcium-independent inducible NOS was transiently expressed in cultured lactotrophs and somatotrophs after the dispersion of cells, but not in GH3 cells and pituitary tissue. This enzyme participated in the control of basal sGC activity in cultured pituitary cells. The overexpression of inducible NOS by lipopolysaccharide + interferon-γ further increased NO and cGMP levels, and the majority of de novo produced cGMP was rapidly released. Addition of an NO donor to perifused pituitary cells also led to a rapid cGMP release. Calcium-mobilizing agonists TRH and GnRH slightly increased basal cGMP production, but only when added in high concentrations. In contrast, adenylyl cyclase agonists GHRH and CRF induced a robust increase in cGMP production, with EC50s in the physiological concentration range. As in cells overexpressing inducible NOS, the stimulatory action of GHRH and CRF was preserved in cells bathed in calcium-deficient medium, but was not associated with a measurable increase in NO production. These results indicate that sGC is present in secretory anterior pituitary cells and is regulated in an NO-dependent manner through constitutively expressed neuronal and endothelial NOS and transiently expressed inducible NOS, as well as independently of NO by adenylyl cyclase coupled-receptors.

Reserpine is a calcium channel antagonist in normal and GH3 rat pituitary cells

1985 ◽  
Vol 248 (1) ◽  
pp. E15-E19
Author(s):  
I. S. Login ◽  
A. M. Judd ◽  
M. J. Cronin ◽  
T. Yasumoto ◽  
R. M. MacLeod
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Anterior Pituitary ◽  
Calcium Uptake ◽  
Calcium Ionophore ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anterior Pituitary Cells

Reserpine exerts direct effects on several tissues, including inhibition of hormone release from rat anterior pituitary cells. To test the hypothesis that reserpine may be acting as a calcium channel antagonist, normal or GH3 rat anterior pituitary cells were preincubated in reserpine or the conventional calcium channel blocker, D-600, followed by exposure to 45Ca2+ together with stimulants of calcium uptake: maitotoxin, a potent calcium channel activator; A23187, a calcium ionophore; or 50 mMK+. After incubation, the cells were harvested by vacuum filtration and cell-associated radioactivity determined. In normal cells, reserpine blocked both basal and K+-stimulated calcium uptake. Reserpine selectively blocked maitotoxin but not A23187-induced calcium uptake. In GH3 cells 9 microM reserpine and 30 microM D-600 were equally effective in blocking maitotoxin-stimulated calcium uptake. Reserpine appears to block voltage-dependent calcium channels in pituitary cells in a concentration-dependent manner but not calcium uptake caused nonspecifically by A23187.

scholarly journals The pockets guide to HLA class I molecules

2021 ◽  
Author(s):  
Andrea T. Nguyen ◽  
Christopher Szeto ◽  
Stephanie Gras
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
Peptide Binding ◽  
Hla Class I ◽  
Class I ◽  
Side Chains ◽  
Binding Prediction ◽  
Peptide Residue ◽  
Hla Class I Molecules ◽  
Binding Pockets

Human leukocyte antigens (HLA) are cell-surface proteins that present peptides to T cells. These peptides are bound within the peptide binding cleft of HLA, and together as a complex, are recognised by T cells using their specialised T cell receptors. Within the cleft, the peptide residue side chains bind into distinct pockets. These pockets ultimately determine the specificity of peptide binding. As HLAs are the most polymorphic molecules in humans, amino acid variants in each binding pocket influences the peptide repertoire that can be presented on the cell surface. Here, we review each of the 6 HLA binding pockets of HLA class I (HLA-I) molecules. The binding specificity of pockets B and F are strong determinants of peptide binding and have been used to classify HLA into supertypes, a useful tool to predict peptide binding to a given HLA. Over the years, peptide binding prediction has also become more reliable by using binding affinity and mass spectrometry data. Crystal structures of peptide-bound HLA molecules provide a means to interrogate the interactions between binding pockets and peptide residue side chains. We find that most of the bound peptides from these structures conform to binding motifs determined from prediction software and examine outliers to learn how these HLAs are stabilised from a structural perspective.

scholarly journals Roles of differential expression of miR-543-5p in GH regulation in rat anterior pituitary cells and GH3 cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222340 ◽  
Author(s):  
Ze-Wen Yu ◽  
Wei Gao ◽  
Xin-Yao Feng ◽  
Jin-Yu Zhang ◽  
Hai-Xiang Guo ◽  
...  
Keyword(s):  
Differential Expression ◽  
Anterior Pituitary ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Anterior Pituitary Cells

scholarly journals EBV BILF1 Evolved To Downregulate Cell Surface Display of a Wide Range of HLA Class I Molecules through Their Cytoplasmic Tail

2013 ◽  
Vol 190 (4) ◽  
pp. 1672-1684 ◽  
Author(s):  
Bryan D. Griffin ◽  
Anna M. Gram ◽  
Arend Mulder ◽  
Daphne Van Leeuwen ◽  
Frans H. J. Claas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Display ◽  
Cytoplasmic Tail ◽  
Hla Class I ◽  
Cell Surface Display ◽  
Class I ◽  
Hla Class I Molecules ◽  
Wide Range

scholarly journals Recognition of Human Histocompatibility Leukocyte Antigen (HLA)-E Complexed with HLA Class I Signal Sequence–derived Peptides by CD94/NKG2 Confers Protection from Natural Killer Cell–mediated Lysis

1998 ◽  
Vol 187 (5) ◽  
pp. 813-818 ◽  
Author(s):  
Francisco Borrego ◽  
Matthias Ulbrecht ◽  
Elisabeth H. Weiss ◽  
John E. Coligan ◽  
Andrew G. Brooks
Keyword(s):  
Cell Surface ◽  
Natural Killer ◽  
Signal Sequence ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Target Cells ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules ◽  
Sequence Position

Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical HLA class I molecule, the gene for which is transcribed in most tissues. It has recently been reported that this molecule binds peptides derived from the signal sequence of HLA class I proteins; however, no function for HLA-E has yet been described. We show that natural killer (NK) cells can recognize target cells expressing HLA-E molecules on the cell surface and this interaction results in inhibition of the lytic process. Furthermore, HLA-E recognition is mediated primarily through the CD94/NKG2-A heterodimer, as CD94-specific, but not killer cell inhibitory receptor (KIR)–specific mAbs block HLA-E–mediated protection of target cells. Cell surface HLA-E could be increased by incubation with synthetic peptides corresponding to residues 3–11 from the signal sequences of a number of HLA class I molecules; however, only peptides which contained a Met at position 2 were capable of conferring resistance to NK-mediated lysis, whereas those having Thr at position 2 had no effect. Interestingly, HLA class I molecules previously correlated with CD94/NKG2 recognition all have Met at residue 4 of the signal sequence (position 2 of the HLA-E binding peptide), whereas those which have been reported not to interact with CD94/NKG2 have Thr at this position. Thus, these data show a function for HLA-E and suggest an alternative explanation for the apparent broad reactivity of CD94/NKG2 with HLA class I molecules; that CD94/NKG2 interacts with HLA-E complexed with signal sequence peptides derived from “protective” HLA class I alleles rather than directly interacting with classical HLA class I proteins.

scholarly journals The gp130 Cytokines Interleukin-11 and Ciliary Neurotropic Factor Regulate through Specific Receptors the Function and Growth of Lactosomatotropic and Folliculostellate Pituitary Cell Lines*

Endocrinology ◽  
2000 ◽  
Vol 141 (5) ◽  
pp. 1746-1753 ◽  
Author(s):  
Carolina Perez Castro ◽  
Alberto Carbia Nagashima ◽  
Marcelo Páez Pereda ◽  
Victoria Goldberg ◽  
Alberto Chervin ◽  
...  
Keyword(s):  
Cell Line ◽  
Messenger Rna ◽  
Anterior Pituitary ◽  
Cell Function ◽  
Pituitary Cell ◽  
Angiogenic Factor ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Anterior Pituitary Cells ◽  
Neurotropic Factor

Abstract Two of the most potent cytokines regulating anterior pituitary cell function are leukemia inhibitory factor and interleukin-6 (IL-6), which belong to the cytokine receptor family using the common gp130 signal transducer. We studied the actions of two other members of this family, IL-11 and ciliary neurotropic factor (CNTF), on folliculostellate (FS) cells (TtT/GF cell line) and lactosomatotropic cells (GH3 cell line). The messenger RNA (mRNA) for the α-chain specific for the IL-11 receptor (1.7 kb) and CNTF receptor (2 kb) are expressed on both cell types. In addition, we detected CNTF receptor mRNA in normal rat anterior pituitary cells. IL-11 (1.25–5 nm) dose dependently stimulated the proliferation of FS cells. CNTF, at doses from 0.4–2 nm, also significantly stimulated the growth of these cells. In addition, both cytokines significantly stimulated proliferation of lactosomatotropic GH3 cells, and CNTF stimulated hormone production (GH and PRL) at 24 h by these cells. At 16–72 h, IL-11 stimulates the secretion of the angiogenic factor vascular endothelial growth factor by FS cells. In addition, both GH3 and FS cells express CNTF mRNA. These data suggest that IL-11 and CNTF may act as growth and regulatory factors in anterior pituitary cells.

scholarly journals Adenoviral vectors encoding tumor necrosis factor-α and FasL induce apoptosis of normal and tumoral anterior pituitary cells

2006 ◽  
Vol 189 (3) ◽  
pp. 681-690 ◽  
Author(s):  
M Candolfi ◽  
G Jaita ◽  
D Pisera ◽  
L Ferrari ◽  
C Barcia ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Line ◽  
Anterior Pituitary ◽  
Tumor Necrosis ◽  
Adenoviral Vectors ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Anterior Pituitary Cells ◽  
Tnf Α ◽  
Necrosis Factor

Our previous work showed that tumor necrosis factor (TNF)-α and FasL induce apoptosis of anterior pituitary cells. To further analyze the effect of these proapoptotic factors, we infected primary cultures from rat anterior pituitary, GH3 and AtT20 cells with first-generation adenoviral vectors encoding TNF-α, FasL or, as a control, β-galactosidase (β-Gal), under the control of the human cytomegalovirus promoter. Successful expression of the encoded transgenes was determined by immunocytochemistry. Although we observed basal expression of TNF-α and FasL in control cultures of anterior pituitary cells, fluorescence-activated cell sorting (FACS) cell cycle analysis showed that the overexpression of TNF-α or FasL increases the percentage of hypodiploid lactotropes and somatotropes. Nuclear morphology and TUNEL staining revealed that the cells undergo an apoptotic death process. We detected strong immunoreactivity for TNFR1 and Fas in the somatolactotrope cell line GH3. TNF-α, but not FasL, was expressed in control cultures of GH3 cells. The infection of GH3 cells with adenovirus encoding TNF-α or FasL increased the percentages of hypodiploid and TUNEL-positive cells. TNF-α or FasL immunoreactivity was not observed in the corticotrope cell line AtT20. However, adenovirus encoding TNF-α or FasL efficiently transduced these cells and increased the percentages of hypodiploid and TUNEL-positive cells. The expression of β-Gal was detected in all these cultures but did not affect cell viability. In conclusion, these results suggest that death signaling cascades triggered by TNF receptor 1 (TNFR1) and Fas are present in both normal and tumoral pituitary cells. Therefore, overexpression of proapoptotic factors could be a useful tool in the therapy of pituitary adenomas.

scholarly journals Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Brogan Yarzabek ◽  
Anita J Zaitouna ◽  
Eli Olson ◽  
Gayathri N Silva ◽  
Jie Geng ◽  
...  
Keyword(s):  
Cell Surface ◽  
Half Life ◽  
Antigen Processing ◽  
Human Lymphocytes ◽  
Hla Class I ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Specific Expression ◽  
Hla Class I Molecules

The highly polymorphic human leukocyte antigen (HLA) class I molecules present peptide antigens to CD8+ T cells, inducing immunity against infections and cancers. Quality control mediated by peptide loading complex (PLC) components is expected to ensure the cell surface expression of stable peptide-HLA class I complexes. This is exemplified by HLA-B*08:01 in primary human lymphocytes, with both expression level and half-life at the high end of the measured HLA-B expression and stability hierarchies. Conversely, low expression on lymphocytes is measured for three HLA-B allotypes that bind peptides with proline at position 2, which are disfavored by the transporter associated with antigen processing. Surprisingly, these lymphocyte-specific expression and stability differences become reversed or altered in monocytes, which display larger intracellular pools of HLA class I than lymphocytes. Together, the findings indicate that allele and cell-dependent variations in antigen acquisition pathways influence HLA-B surface expression levels, half-lives and receptivity to exogenous antigens.

Flow cytometric analysis of functional anterior pituitary cells from female rats

1990 ◽  
Vol 126 (2) ◽  
pp. 261-NP ◽  
Author(s):  
D. Wynick ◽  
M. S. Venetikou ◽  
R. Critchley ◽  
J. M. Burrin ◽  
S. R. Bloom
Keyword(s):  
Cell Surface ◽  
Cell Size ◽  
Anterior Pituitary ◽  
Laser Light ◽  
Female Rats ◽  
Pituitary Cells ◽  
Light Scatter ◽  
Cell Sorter ◽  
Anterior Pituitary Cells ◽  
Surface Labelling

ABSTRACT Laser-light scatter signals generated from living cells provide useful information with regard to both cell size (forward-angle light scatter) and granularity (ninety-degree or perpendicular light scatter). By measuring angles of light scatter and fluorescence, a fluorescence-activated cell sorter is capable of analysing and sorting cells on the basis of their size, granularity and cell-surface fluorescence. Using an electronically programmable individual cell sorter we were able to analyse single, viable, dispersed anterior pituitary cells of the female rat on the basis of their laser light scatter characteristics. Two distinct populations of differing granularity were defined: 26±2·2% (mean ± s.e.m.) were more granular and 74±3·5% less granular. Acutely dispersed anterior pituitary cells were labelled with antibodies against four of the anterior pituitary hormones, and cell size and granularity were compared amongst the different hormonal cell types. Somatotrophs were the most granular cell type, gonadotrophs were the largest and corticotrophs the smallest, whilst lactotrophs were of intermediate size. Labelling was demonstrated to be dependent upon the secretory state of the cell. Hypothalamic stimulating factors increased cell-surface labelling, whilst dopamine and somatostatin decreased labelling. These changes compare favourably with published data obtained by immunocytochemistry. Using dual-colour fluorescence cell surface labelling we were unable to define a population of cells secreting both prolactin and growth hormone (mammosomatotrophs). Journal of Endocrinology (1990) 126, 261–268

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