scholarly journals Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells

2008 ◽  
Vol 413 (3) ◽  
pp. 467-478 ◽  
Author(s):  
Paola Matarrese ◽  
Valeria Manganelli ◽  
Tina Garofalo ◽  
Antonella Tinari ◽  
Lucrezia Gambardella ◽  
...  
Keyword(s):  
Cell Death ◽  
Cross Talk ◽  
Fas Ligand ◽  
Type Ii Cells ◽  
Type Ii ◽  
Ligand Interaction ◽  
Directional Movement ◽  
Type Ii Cell ◽  
Endocytic Vesicles

Participation of diverse organelles in the intracellular signalling that follows CD95/Fas receptor ligation encompasses a series of subcellular changes that are mandatory for, or even bolster, the apoptotic cascade. In the present study, we analysed the role of endocytosis in the propagation of cell death signalling after CD95/Fas engagement in type II cells (CEM cells). We show that this receptor–ligand interaction triggers endocytosis independently of any caspase activation. This FasL (Fas ligand)-induced endocytosis also leads to an early and directional ‘movement’ of endocytic vesicles towards the mitochondrial compartment. In turn, this cross-talk between endosomal and mitochondrial compartments was followed by the loss of the mitochondrial membrane potential and apoptosis execution. This cell remodelling was absent in receptor-independent cell death, such as that induced by the mitochondriotropic drug staurosporine, and in a CEM cell line selected for its multidrug resistance (CEM VBL100). In these cells a reduced FasL (Fas ligand)-induced endocytosis and a reduced organelle cross-talk corresponded to a reduced apoptosis. Altogether, these findings suggest a key role of endocytosis in the propagation and amplification of the CD95/Fas-activated signalling leading to type II cell demise.

scholarly journals sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2177
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Dmytro Petukhov ◽  
Ronit Ahdut-HaCohen ◽  
Mark Richter-Dayan ◽  
Raphael Breuer
Keyword(s):  
Cell Death ◽  
Lung Disease ◽  
Fas Ligand ◽  
Death Receptor ◽  
Mesenchymal Cells ◽  
Soluble Form ◽  
Cell Accumulation ◽  
Key Factor ◽  
Aged Subjects

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.

P2u purinoceptor stimulation of surfactant secretion coupled to phosphatidylcholine hydrolysis in type II cells

1994 ◽  
Vol 267 (5) ◽  
pp. L625-L633 ◽  
Author(s):  
L. I. Gobran ◽  
Z. X. Xu ◽  
Z. Lu ◽  
S. A. Rooney
Keyword(s):  
Phospholipase D ◽  
Receptor Gene ◽  
Primary Cultures ◽  
Cell Receptor ◽  
Northern Analysis ◽  
Type Ii Cells ◽  
Type Ii ◽  
Type Ii Cell ◽  
Subsequent Activation ◽  
Phosphatidylcholine Secretion

ATP is known to stimulate surfactant phospholipid secretion in type II cells, and there is evidence that this effect is mediated by a P2 purinoceptor. At least five subtypes of the P2 receptor have been reported, but it is not clear which one exists on the type II cell. To determine whether it is the P2u subtype, at which UTP is equipotent with ATP, we have compared the effects of ATP and UTP on phosphatidylcholine secretion and second messenger formation in primary cultures of rat type II cells. ATP and UTP were equally potent in stimulating phosphatidylcholine secretion and phospholipase D activation. The potency order, UTP = ATP > ADP > 2-methylthio-ATP, was the same as that reported for the P2u receptor. UTP stimulated diacylglycerol and phosphatidic acid formation to the same extent as ATP. ATP also increased choline formation. Formation of diacylglycerol was biphasic, and the first peak in response to ATP was previously shown to be associated with inositol trisphosphate formation. Northern analysis showed that the P2u receptor gene was expressed to a greater extent in type II cells than in whole lung. These data suggest that ATP and UTP act via a P2u receptor that is coupled to phosphoinositide-specific phospholipase C with subsequent activation of phospholipase D acting on phosphatidylcholine. ATP has also been reported to act at an additional type II cell receptor coupled to adenylate cyclase. In contrast, UTP did not promote adenosine 3',5'-cyclic monophosphate formation and therefore does not act at that receptor.

Sulfation of extracellular matrices modifies responses of alveolar type II cells to fibroblast growth factors

1996 ◽  
Vol 271 (5) ◽  
pp. L688-L697 ◽  
Author(s):  
P. L. Sannes ◽  
J. Khosla ◽  
P. W. Cheng
Keyword(s):  
Growth Factors ◽  
Biological Significance ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Fibroblast Growth ◽  
Alveolar Type Ii Cells ◽  
Proliferation And Differentiation ◽  
Type Ii Cell

The pulmonary alveolar basement membrane (BM) associated with alveolar type II cells has been shown to be significantly less sulfated than that of type I cells. To examine the biological significance of this observation, we measured the incorporation of 5-bromodeoxyuridine (BrdU) as an indicator of DNA synthesis in isolated rat type II cells cultured for 72-120 h on substrata that were naturally sulfated, not sulfated, or chemically desulfated in serum-free, hormonally defined media, with and without selected growth factors. The percentage of cells incorporating BrdU was significantly elevated by desulfated chondroitin sulfate in the presence of fibroblast growth factor-2 (FGF-2 or basic FGF) and depressed by heparin in the presence of either FGF-1 or acidic FGF or FGF-2. This depressive effect was lost by removing sulfate from the heparin. Some responses were dependent on the period of time in culture and concentration and molecular weight of the substrata. These observations support the notion that sulfation per se of certain components of BM is a key determinant of type II cell responses to select growth factors that may define patterns of proliferation and differentiation.

Development of type II pneumocytes in rat lung

1991 ◽  
Vol 260 (2) ◽  
pp. L113-L122 ◽  
Author(s):  
S. L. Young ◽  
E. K. Fram ◽  
C. L. Spain ◽  
E. W. Larson
Keyword(s):  
Three Dimensional ◽  
Alveolar Epithelium ◽  
Type Ii Cells ◽  
Type Ii ◽  
Time Period ◽  
Type Ii Pneumocytes ◽  
Type Ii Cell ◽  
Membrane Type ◽  
Cytoplasmic Processes ◽  
Homogenous Population

At a late stage of fetal development, the mammalian alveolar epithelium undergoes an abrupt differentiation as a part of the preparation of the lung for the postnatal demands of gas exchange. Some of the most striking changes occur in the type II pneumocytes as they lose their glycogen and start to produce the lamellated inclusion granules that contain pulmonary surfactant. Premature birth before adequate type II cell maturation results in the neonatal respiratory distress syndrome, which is frequently fatal. We have used serial ultrathin sectioning, electron microscopy, and three-dimensional reconstructions to study the ultrastructural features of maturation of rat type II cells from a single rat each at age gestational day 20 through adult stages. We found evidence over this time span for compartmentation of several secretory granule precursors within type II cells. Changes in the polarization of lamellar bodies were observed over the time period studied. We also found marked gestational changes in the number and morphology of type II cell cytoplasmic processes that perforate the basement membrane. Type II cell mitochondria changed in shape during postnatal development from single, spherical to complex, branched structures. Volume composition obtained from serial sections of a small number of type II cells agreed closely with published morphometric data, indicating that throughout the animal's lifespan, type II cells are a homogenous population.

scholarly journals Restoration of Defective Cross Talk in ssi2 Mutants: Role of Salicylic Acid, Jasmonic Acid, and Fatty Acids in SSI2-Mediated Signaling

2003 ◽  
Vol 16 (11) ◽  
pp. 1022-1029 ◽  
Author(s):  
Pradeep Kachroo ◽  
Aardra Kachroo ◽  
Ludmila Lapchyk ◽  
David Hildebrand ◽  
Daniel F. Klessig
Keyword(s):  
Cell Death ◽  
Salicylic Acid ◽  
Jasmonic Acid ◽  
Cross Talk ◽  
Pr Genes ◽  
Exogenous Application ◽  
Basal Level Expression ◽  
Sa Signaling ◽  
Spontaneous Cell Death

The Arabidopsis mutants ssi2 and fab2 are defective in stearoyl ACP desaturase, which causes altered salicylic acid (SA)- and jasmonic acid (JA)-mediated defense signaling. Both ssi2 and fab2 plants show spontaneous cell death, express PR genes constitutively, accumulate high levels of SA, and exhibit enhanced resistance to bacterial and oomycete pathogens. In contrast to constitutive activation of the SA pathway, ssi2 and fab2 plants are repressed in JA-mediated induction of the PDF1.2 gene, which suggests that the SSI2-mediated signaling pathway modulates cross talk between the SA and JA pathways. In this study, we have characterized two recessive nonallelic mutants in the ssi2 background, designated as rdc (restorer of defective cross talk) 2 and rdc8. Both ssi2 rdc mutants are suppressed in constitutive SA signaling, show basal level expression of PR-1 gene, and induce high levels of PDF1.2 in response to exogenous application of JA. Interestingly, while the rdc8 mutation completely abolishes spontaneous cell death in ssi2 rdc8 plants, the ssi2 rdc2 plants continue to show some albeit reduced cell death. Fatty acid (FA) analysis showed a reduction in 16:3 levels in ssi2 rdc8 plants, which suggests that this mutation may limit the flux of FAs into the pro-karyotic pathway of glycerolipid biosynthesis. Both rdc2 and rdc8 continue to accumulate high levels of 18:0, which suggests that 18:0 levels were responsible for neither constitutive SA signaling nor repression of JA-induced expression of the PDF1.2 gene in ssi2 plants. We also analyzed SA and JA responses of the fab2-derived shs1 mutant, which accumulates levels of 18:0 over 50% lower than those in the fab2 plants. Even though fab2 shs1 plants were morphologically bigger than fab2 plants, they expressed PR genes constitutively, showed HR-like cell death, and accumulated elevated levels of SA. However, unlike the ssi2 rdc plants, fab2 shs1 plants were unable to induce high levels of PDF1.2 expression in response to exogenous application of JA. Together, these results show that defective cross talk in ssi2 can be restored by second site mutations and is independent of morphological size of the plants, cell death, and elevated levels of 18:0.

Nitric oxide alters metabolism in isolated alveolar type II cells

1996 ◽  
Vol 271 (1) ◽  
pp. L23-L30 ◽  
Author(s):  
P. R. Miles ◽  
L. Bowman ◽  
L. Huffman
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Atp Synthesis ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Atp Content ◽  
Alveolar Type Ii Cells ◽  
Type Ii Cell ◽  
Cellular Oxygen

Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells.

Enhanced alveolar type II cell growth on a pulmonary extracellular matrix over fibroblasts

1997 ◽  
Vol 272 (3) ◽  
pp. L413-L417 ◽  
Author(s):  
I. Y. Adamson ◽  
L. Young ◽  
J. Bakowska
Keyword(s):  
Extracellular Matrix ◽  
Cell Growth ◽  
Growth Effect ◽  
Lung Fibroblasts ◽  
Cell Contact ◽  
Alveolar Type ◽  
Thymidine Uptake ◽  
Type Ii Cells ◽  
Type Ii ◽  
Type Ii Cell

The growth of alveolar type II cells was studied when these cells were maintained for 2 days on a pulmonary endothelium-derived extracellular matrix (ECM) on a filter with or without lung fibroblasts in the lower chambers of culture wells. Type II cell proliferation was enhanced by the ECM compared with other substrates but was significantly higher with fibroblasts beneath. This was determined by thymidine uptake and cell numbers. The diffusing factor from fibroblasts appeared to be keratinocyte growth factor (KGF), because this cytokine increased type II cell growth in culture and the neutralizing antibody to KGF blocked the observed fibroblast-induced growth increase. None of the antibodies to various cytokines had any effect on the ECM-induced proliferation. Although the type II cells were shown to produce degradative activity for the ECM, there was little secreted enzyme activity in supernatants and there was no demonstrated autocrine-regulated growth effect. The results suggest that type II cell growth may be stimulated by both 1) a matrix-bound factor that acts through a cell contact-mediated process, and 2) a fibroblast-secreted factor that appears to be KGF.

The Critical Role of Fas-Fas Ligand Interaction in Donor-Specific Transfusion-Induced Tolerance to H-Y Antigen

2004 ◽  
Vol 78 (6) ◽  
pp. 799-806 ◽  
Author(s):  
Ryosuke Minagawa ◽  
Shinji Okano ◽  
Yukihiro Tomita ◽  
Kenji Kishihara ◽  
Hisakata Yamada ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Critical Role ◽  
Ligand Interaction ◽  
Induced Tolerance

A noninducible cystine transport system in rat alveolar type II cells

1995 ◽  
Vol 268 (1) ◽  
pp. L21-L26 ◽  
Author(s):  
D. M. Bukowski ◽  
S. M. Deneke ◽  
R. A. Lawrence ◽  
S. G. Jenkinson
Keyword(s):  
Transport System ◽  
Cell Types ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Epithelial ◽  
Sodium Dependent ◽  
Type Ii Cell ◽  
Rate Limiting

Type II lung epithelial cells are different from other lung cell types in their means of processing and regulating intracellular glutathione (GSH) levels. In lung cell types, including endothelial cells, fibroblasts, smooth muscle cells, and macrophages, oxidants, sulfhydryl reagents, and electrophilic agents have been shown to induce cystine uptake and concomitantly increase GSH levels, suggesting that cysteine, formed by intracellular reduction of cystine, is a rate-limiting substrate for GSH synthesis. The cystine transport increase was reportedly due to increase in activity of a sodium-independent transport system designated xc-. We have now examined cultures of rat lung type II cells exposed to diethylmaleic acid and arsenite. Although a rise in cellular GSH occurred, cystine transport was not induced. Cystine transport in type II cells was found to differ from the xc- system previously described. Type II cell cystine transport is primarily sodium dependent and is inhibitable by aspartate as well as glutamate and homocysteate. We conclude that the type II cell differs from other lung cell types in both its cystine transport mechanism and method of GSH regulation.

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