scholarly journals Pathways followed by membrane recovered from the surface of plasma cells and myeloma cells

1980 ◽  
Vol 152 (1) ◽  
pp. 1-19 ◽  
Author(s):  
PD Ottosen ◽  
PJ Courtoy ◽  
MG Farquhar
Keyword(s):  
Secretory Pathway ◽  
Plasma Cells ◽  
Surface Membrane ◽  
Secretory Cells ◽  
Secretory Product ◽  
Vesicle Membrane ◽  
Myeloma Cells ◽  
Glandular Cells ◽  
Lysosomal System ◽  
Endocytic Vesicles

Evidence for recovery of surface membrane and its fusion with Golgi cisternae has been obtained previously in several glandular cells. This study was conducted to determine whether or not membrane is similarly retrieved from the surfaces of plasma cells from lymph nodes (of rats immunized with horseradish peroxidase [HRP]) and mouse myeloma cells (RPC 5.4 and X63 Ag 8 cell lines). Electron-dense tracers (cationic and anionic ferritin, HRP) were used to trace the pathways followed by surface membrane recovered by endocytosis, and immunocytochemistry was used to identify the secretory compartments. When plasma cells or myeloma cells were incubated with cationized ferritin (CF), it bound to the cell surfaces and was taken up in endocytic vesicles, for the most part bound to the vesicle membrane. After 30-60 min, it was found increasingly within lysosomes and in several secretory compartments- notably in multiple stacked Golgi cisternae and secretory vacuoles. By immunocytochemistry the secretory product (immunoglobulins) and CF could be demonstrated in the same Golgi components. When myeloma cells were incubated with native (anionic) ferritin or in HRP, these tracers were taken up in much smaller amounts, primarily within the contents of endocytic vesicles. With continued incubation, they appeared only in lysosomes. When cells were doubly incubated, first in CF and then in HRP, both tracers were taken up (often within the same endocytic vesicle), but they maintained their same destinations as when incubated in a single tracer alone: the content marker, HRP, was localized exclusively within the lysosomal system, whereas the membrane marker, CF, was found within elements along the secretory pathway as well as within lysosomes. The findings demonstrate the existence of considerable membrane traffic between the cell membrane and the Golgi cisternae and lysosomes in both normal plasma cells and myeloma cells. Because myeloma cells behave like the glandular cells studied previously with regard to pathways of retrieved surface membrane, they represent a suitable and promising system for further studies of mechanisms and pathways of membrane retrieval and recycling in secretory cells.

Endocytosis in secretory cells

1981 ◽  
Vol 296 (1080) ◽  
pp. 67-72 ◽  
Keyword(s):  
Plasma Membrane ◽  
Exocrine Pancreas ◽  
Apical Cell ◽  
Secretory Cells ◽  
Cell Surfaces ◽  
Secretory Cycle ◽  
Secretion Granules ◽  
Glandular Cells ◽  
Endocytic Vesicles ◽  
Indirect Route

Membranes of secretion granules inserted during exocytosis into the luminal plasma membrane of glandular cells are retrieved by endocytosis as revealed by electron dense tracers applied selectively to the apical cell surfaces. Two major pathways that endocytic vesicles may take are described: (1) a direct route to the Golgi complex (e.g. in parotid and exocrine pancreas) with later appearance of the tracer in the periphery of mature secretion granules; (2) an indirect route with lysosomes as a first station and the subsequent appearance of tracer in stacked Golgi cisternae. It is presumed that some of the retrieved membrane follows the same pathways and is reutilized in the secretory cycle.

scholarly journals Recovery of surface membrane in anterior pituitary cells. Variations in traffic detected with anionic and cationic ferritin

1978 ◽  
Vol 77 (3) ◽  
pp. R35 ◽  
Author(s):  
MG Farquhar
Keyword(s):  
Anterior Pituitary ◽  
Secretory Pathway ◽  
Negative Charge ◽  
Positive Charge ◽  
Surface Membrane ◽  
Pituitary Cells ◽  
Net Charge ◽  
Secretion Granules ◽  
Lysosomal System ◽  
Net Positive Charge

Cells dissociated from rat anterior pituitaries were incubated with native or cationized ferritin (CF) to trace the fate of surface membrane. Native ferritin, which did not bind to the cell surface, was taken up in small amounts by bulk-phase endocytosis and was found increasingly (over 1-2 h) concentrated in lysosomes. CF at 100-fold less concentrations bound rapidly to the cell membrane, was taken up by endocytosis in far greater amounts, and within 15-60 min was found increasingly within multiple stacked Golgi cisternae, around forming secretion granules, and within elements of GERL, as well as within lysosomes. The findings demonstrate that the fate of the tracer--and presumably also that of the surface membrane--varies with the same molecule differing only in net charge: vesicles carrying anionic ferritin (net negative charge) fuse only with elements of the lysosomal system whereas those carrying CF (net positive charge) can fuse not only with elements of the lysosomal system, but also with elements along the secretory pathway (Golgi cisternae and condensing granules) as well.

Ultrastructure of scent glands in larvae of Apateticus bracteatus (Hemiptera: Pentatomidae) and chemical composition of the secretion

1980 ◽  
Vol 58 (11) ◽  
pp. 2105-2115 ◽  
Author(s):  
Jean Percy ◽  
J. A. MacDonald ◽  
J. Weatherston
Keyword(s):  
Chemical Composition ◽  
Interstitial Cells ◽  
Secretory Cells ◽  
Scent Glands ◽  
Volatile Constituents ◽  
Dorsal Wall ◽  
Anterior Dorsal ◽  
Glandular Cells ◽  
Gland Function ◽  
Dorsal Abdominal Glands

The three dorsal abdominal glands in larvae of Apateticus bracteatus (Pentatomidae) secrete a mixture of compounds. Major volatile constituents of the secretion are identified, herein, as tridecane and 2-octenal. There are also trace amounts of 2-hexenal and two other unidentified compounds.Each of the glands has paired orifices that are located between tergites 3/4, 4/5, and 5/6, but only the most anterior gland is paired. In anterior glands of midinstar larvae, glandular cells associated with ducts, and interstitial glandular cells are distributed along the ventral walls of the reservoirs. In posterior glands, columnar glandular cells are located in the anterior dorsal wall of the reservoirs; secretory cells associated with ducts, and nonglandular interstitial cells are distributed throughout the ventral and posterior walls of the reservoirs. The interstitial glandular cells of the anterior gland and the columnar glandular cells of the middle and posterior glands contain cytoplasmic organelles characteristic of lipid-producing cells. In all glands the secretory cells associated with ducts secrete lipids. Evidence indicating the importance of Golgi and ER in secretion synthesis is presented. The reservoirs and ducts have a thin cuticular lining.The bearing of the results on present ideas of gland function in Heteroptera is discussed.

Experimental Data on the Function of the Interstitium of the Gonads: Experiments with Cockerels

1947 ◽  
Vol s3-88 (2) ◽  
pp. 135-150
Author(s):  
J. W. SLUITER ◽  
G. J. VAN OORDT
Keyword(s):  
Experimental Data ◽  
Connective Tissue ◽  
Leydig Cells ◽  
Cell Types ◽  
Sex Hormone ◽  
Secretory Cells ◽  
Secretory Function ◽  
Glandular Cells ◽  
Male Sex ◽  
Secondary Function

1. The relative volumes of the testes and their components of 31 cockerels, 2-200 days old, were calculated and compared with the size of their increasing head appendages (Text-figs. 1a-d, 2); in addition, the effect of gestyl-administration on testes of cockerels of this age was investigated. 2. Several types of interstitial testis-cells could be distinguished morphologically and physiologically (Text-figs. 3-6 and Pl. 1); these cell-types were studied with different techniques and counted separately. 3. The main types of the interstitial cells are: (a) Lipoid cells, totally packed with lipoid globules. These cells, which are considered by many authors as fully developed Leydig cells, are not directly connected with the production of the male sex hormone; perhaps they have a secondary function in this respect, as cholesterolderivatives are stored in these cells (Pl. 1, Text-fig. 3a). (b) Secretory cells, characterized by the absence of lipoid vacuoles and the presence of numerous granular and filamentous mitochondria. These secretory cells, which produce the male sex hormone, can be divided into secretory cells A (Text-fig. 6a) without, and secretory cells B with, one large vacuole (Text-figs. 6b, 6c, 6d). 4. A considerable and partly intercellular storage of lipoids may take place at any age in the intertubular connective tissue (Text-figs. 3-4 and Pl. 1). 5. The number of the lipoid cells depends on the nutritive conditions of the animal and the development of its testes (Text-fig. 7). 6. In older cockerels most of the glandular cells lose their secretory function and pass over into lipoid storing cells. 7. Therefore we agree with Benoit, when he denies the occurrence of a ‘secretion de luxe’, but we cannot accept the presence of a ‘parenchyme de luxe’ in the testes of older cockerels.

scholarly journals Hypoxia promotes IL-32 expression in myeloma cells, and high expression is associated with poor survival and bone loss

2017 ◽  
Vol 1 (27) ◽  
pp. 2656-2666 ◽  
Author(s):  
Muhammad Zahoor ◽  
Marita Westhrin ◽  
Kristin Roseth Aass ◽  
Siv Helen Moen ◽  
Kristine Misund ◽  
...  
Keyword(s):  
Bone Loss ◽  
Proinflammatory Cytokine ◽  
Plasma Cells ◽  
Bone Destruction ◽  
High Expression ◽  
Poor Survival ◽  
Myeloma Cells ◽  
Key Points

Key Points IL-32 is a proinflammatory cytokine expressed by plasma cells in a subset of MM patients, and high expression correlates with poor survival. IL-32 is induced by hypoxia and secreted from MM cells in EVs that promote bone destruction.

Inhibition of protein geranylgeranylation induces apoptosis in myeloma plasma cells by reducing Mcl-1 protein levels

Blood ◽  
2003 ◽  
Vol 102 (9) ◽  
pp. 3354-3362 ◽  
Author(s):  
Niels W. C. J. van de Donk ◽  
Marloes M. J. Kamphuis ◽  
Berris van Kessel ◽  
Henk M. Lokhorst ◽  
Andries C. Bloem
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Mevalonate Pathway ◽  
Cytochrome C Release ◽  
Hmg Coa Reductase ◽  
Myeloma Cells ◽  
Protein Levels ◽  
Geranylgeranyl Transferase ◽  
Induced Apoptosis ◽  
Coa Reductase

AbstractHMG-CoA reductase is the rate-limiting enzyme of the mevalonate pathway leading to the formation of cholesterol and isoprenoids such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP). The inhibition of HMG-CoA reductase by lovastatin induced apoptosis in plasma cell lines and tumor cells from patients with multiple myeloma. Here we show that cotreatment with mevalonate or geranylgeranyl moieties, but not farnesyl groups, rescued myeloma cells from lovastatin-induced apoptosis. In addition, the inhibition of geranylgeranylation by specific inhibition of geranylgeranyl transferase I (GGTase I) induced the apoptosis of myeloma cells. Apoptosis triggered by the inhibition of geranylgeranylation was associated with reduction of Mcl-1 protein expression, collapse of the mitochondrial transmembrane potential, expression of the mitochondrial membrane protein 7A6, cytochrome c release from mitochondria into the cytosol, and stimulation of caspase-3 activity. These results imply that protein geranylgeranylation is critical for regulating myeloma tumor cell survival, possibly through regulating Mcl-1 expression. Our results show that pharmacologic agents such as lovastatin or GGTase inhibitors may be useful in the treatment of multiple myeloma.

scholarly journals The secretory pathway of bovine platelets

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 878-885 ◽  
Author(s):  
JG White
Keyword(s):  
Plasma Membrane ◽  
Secretory Pathway ◽  
Human Platelet ◽  
Surface Membrane ◽  
Surrounding Medium ◽  
Human Platelets ◽  
Resting Cells ◽  
Granule Secretion ◽  
New Perspective ◽  
Platelet Secretion

Abstract Human platelets contain tortuous channels in their cytoplasm, the surface-connected or open canalicular system (OCS), that communicate directly with the surrounding medium through openings on the surface membrane. Some workers have suggested that the OCS serves as the egress route for products secreted during the release reaction. Others have proposed alternate secretory pathways. Since bovine platelets lack the OCS found in human cells, the present study has examined the secretory mechanism of these cells to see whether it can shed light on the mystery of human platelet secretion. Bovine platelet granules, in contrast to human granules, are located more peripherally in resting cells (often in contact with the plasma membrane), most do not move centrally following thrombin stimulation as do human platelet granules, and many fuse directly with the external plasma membrane without any intermediate channel. The lack of peripheral location of human granules, their central rather than peripheral movement during secretion, and the presence of extensive channels are all consistent with the larger importance of the secretory channel to human platelets. Thus, though studies of bovine secretion do show that platelets can secrete their granules by direct fusion of granule and surface membranes, other differences from human platelets emphasize that this pathway, although important to bovine platelet secretion, is less important in human platelets. Studies of bovine platelets also show that the OCS is more dynamic than might have been considered from human studies and can form rapidly in response to stimulation. Such newly formed channels are used as a conduit for secretion of granule contents. The finding emphasizes the importance of channels for granule secretion in platelets generally and puts a new perspective on the ability of these cells to form channels rapidly in response to stimulation.

scholarly journals Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1542-1549 ◽  
Author(s):  
AF Gazdar ◽  
HK Oie ◽  
IR Kirsch ◽  
GF Hollis
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cultured Cells ◽  
Human Cell Line ◽  
Defined Medium ◽  
Chromosome 8 ◽  
Nuclear Antigen ◽  
Secretory Cells

Using a serum-free defined medium, we have established a human cell line, NCI-H929, from a malignant effusion occurring in a patient with IgAk myeloma. The cultured cells have the morphologic, ultrastructural, biochemical, immunologic, and cytochemical features of plasma cells. The cells have rearranged alpha and kappa genes and synthesize and secrete high amounts of IgAk (greater than 80 micrograms/10(6) cells per 24 hours). The cells express surface immunoglobulin (alpha and kappa), the plasma cell antigen PCA-1, the transferrin receptor (T9) and T10 but lack antigens associated with earlier stages of B cell development (HLA-DR, B1, B2, B4, CALLA), as well as other leukocyte- macrophage antigens and Epstein-Barr virus (EBV) nuclear antigen. Although molecular studies confirm that both the tumor and cultured cells are derived from the same clone of malignant B cells, the tumor cells were predominantly near-diploid, whereas the cultured cells are predominantly near-tetraploid with six copies of chromosome 8, four to six of which have an 8q + abnormality. However, both the tumor and the cultured cells have a rearrangement of the cellular c-myc proto- oncogene (located at 8q24) and express c-myc RNA. Although a modest number of human “plasmacytoid” cell lines have been established, most are lymphoblastoid lines lacking plasma cell features, while others appear to be early secretory cells. In contrast, NCI-H929 is a differentiated, highly secretory human plasma cell line.

scholarly journals Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Laurie Herviou ◽  
Sara Ovejero ◽  
Fanny Izard ◽  
Ouissem Karmous-Gadacha ◽  
Claire Gourzones ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Myeloma Cell ◽  
Histone H4 ◽  
Myeloma Cells ◽  
Functional Studies ◽  
Replicative Stress ◽  
Poor Outcome ◽  
Subsequent Decrease ◽  
Lysine Methyltransferase

Abstract Background Multiple myeloma (MM) is a malignancy of plasma cells that largely remains incurable. The search for new therapeutic targets is therefore essential. In addition to a wide panel of genetic mutations, epigenetic alterations also appear as important players in the development of this cancer, thereby offering the possibility to reveal novel approaches and targets for effective therapeutic intervention. Results Here, we show that a higher expression of the lysine methyltransferase SETD8, which is responsible for the mono-methylation of histone H4 at lysine 20, is an adverse prognosis factor associated with a poor outcome in two cohorts of newly diagnosed patients. Primary malignant plasma cells are particularly addicted to the activity of this epigenetic enzyme. Indeed, the inhibition of SETD8 by the chemical compound UNC-0379 and the subsequent decrease in histone H4 methylation at lysine 20 are highly toxic in MM cells compared to normal cells from the bone marrow microenvironment. At the molecular level, RNA sequencing and functional studies revealed that SETD8 inhibition induces a mature non-proliferating plasma cell signature and, as observed in other cancers, triggers an activation of the tumor suppressor p53, which together cause an impairment of myeloma cell proliferation and survival. However, a deadly level of replicative stress was also observed in p53-deficient myeloma cells treated with UNC-0379, indicating that the cytotoxicity associated with SETD8 inhibition is not necessarily dependent on p53 activation. Consistent with this, UNC-0379 triggers a p53-independent nucleolar stress characterized by nucleolin delocalization and reduction of nucleolar RNA synthesis. Finally, we showed that SETD8 inhibition is strongly synergistic with melphalan and may overcome resistance to this alkylating agent widely used in MM treatment. Conclusions Altogether, our data indicate that the up-regulation of the epigenetic enzyme SETD8 is associated with a poor outcome and the deregulation of major signaling pathways in MM. Moreover, we provide evidences that myeloma cells are dependent on SETD8 activity and its pharmacological inhibition synergizes with melphalan, which could be beneficial to improve MM treatment in high-risk patients whatever their status for p53.

scholarly journals The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression

1998 ◽  
Vol 187 (8) ◽  
pp. 1169-1178 ◽  
Author(s):  
Christophe Arpin ◽  
Odette de Bouteiller ◽  
Diane Razanajaona ◽  
Isabelle Fugier-Vivier ◽  
Francine Brière ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Light Chain ◽  
Germinal Center ◽  
Plasma Cells ◽  
Precursor Cells ◽  
Memory B Cells ◽  
Hematopoietic Stem ◽  
Myeloma Cells ◽  
Λ Light Chain

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.

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