Ethanol Inhibition of Cell-Mediated Lysis of Antibody-Sensitized Target Cells at a Calcium-Dependent Step

1989 ◽  
Vol 192 (2) ◽  
pp. 177-181 ◽  
Author(s):  
A. S. Walia ◽  
E. W. Lamon
Keyword(s):  
Target Cells ◽  
Ethanol Inhibition ◽  
Calcium Dependent

scholarly journals Cryptosporidium parvum Subtilisin-Like Serine Protease (SUB1) Is Crucial for Parasite Egress from Host Cells

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Samantha Nava ◽  
A. Clinton White ◽  
Alejandro Castellanos-González
Keyword(s):  
Life Cycle ◽  
Serine Protease ◽  
Host Cells ◽  
Effective Vaccine ◽  
Infection Model ◽  
Target Cells ◽  
Calcium Dependent ◽  
Argonaute 2 ◽  
Parasite Egress

ABSTRACT Despite the severity and global burden of Cryptosporidium infection, treatments are less than optimal, and there is no effective vaccine. Egress from host cells is a key process for the completion of the life cycle of apicomplexan parasites. For Plasmodium species, subtilisin-like serine protease (SUB1) is a key mediator of egress. For Toxoplasma species, calcium-dependent protein kinases (CDPKs) are critical. In this study, we characterized Cryptosporidium SUB1 expression and evaluated its effect using an infection model. We found increased expression between 12 and 20 h after in vitro infection, prior to egress. We induced silencing of SUB1 (ΔSUB1) mRNA using SUB1 single-stranded antisense RNA coupled with human Argonaute 2. Silencing of SUB1 mRNA expression did not affect parasite viability, excystation, or invasion of target cells. However, knockdown led to a 95% decrease in the proportion of released merozoites in vitro (P < 0.0001). In contrast, silencing of CDPK5 had no effect on egress. Overall, our results indicate that SUB1 is a key mediator of Cryptosporidium egress and suggest that interruption of the life cycle at this stage may effectively inhibit the propagation of infection.

scholarly journals Ethanol inhibition of NMDA receptors in calcium-dependent and –independent modes

2020 ◽  
Vol 522 (4) ◽  
pp. 1046-1051
Author(s):  
Sergei I. Boikov ◽  
Dmitry A. Sibarov ◽  
Sergei M. Antonov
Keyword(s):  
Nmda Receptors ◽  
Ethanol Inhibition ◽  
Calcium Dependent

scholarly journals The Functional Basis for Hemophagocytic Lymphohistiocytosis in a Patient with Co-inherited Missense Mutations in the Perforin (PFN1) Gene

2004 ◽  
Vol 200 (6) ◽  
pp. 811-816 ◽  
Author(s):  
Ilia Voskoboinik ◽  
Marie-Claude Thia ◽  
Annette De Bono ◽  
Kylie Browne ◽  
Erika Cretney ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Lipid Membranes ◽  
Secretory Granules ◽  
Leukemia Cells ◽  
Target Cells ◽  
Dependent Manner ◽  
Missense Mutations ◽  
Calcium Dependent ◽  
Immunodeficiency Disorder ◽  
Rbl Cells

About 30% of cases of the autosomal recessive immunodeficiency disorder hemophagocytic lymphohistiocytosis are believed to be caused by inactivating mutations of the perforin gene. We expressed perforin in rat basophil leukemia cells to define the basis of perforin dysfunction associated with two mutations, R225W and G429E, inherited by a compound heterozygote patient. Whereas RBL cells expressing wild-type perforin (67 kD) efficiently killed Jurkat target cells to which they were conjugated, the substitution to tryptophan at position 225 resulted in expression of a truncated (∼45 kD) form of the protein, complete loss of cytotoxicity, and failure to traffic to rat basophil leukemia secretory granules. By contrast, G429E perforin was correctly processed, stored, and released, but the rat basophil leukemia cells possessed reduced cytotoxicity. The defective function of G429E perforin mapped downstream of exocytosis and was due to its reduced ability to bind lipid membranes in a calcium-dependent manner. This study elucidates the cellular basis for perforin dysfunctions in hemophagocytic lymphohistiocytosis and provides the means for studying structure–function relationships for lymphocyte perforin.

scholarly journals A calcium- and perforin-independent pathway of killing mediated by murine cytolytic lymphocytes.

1987 ◽  
Vol 166 (6) ◽  
pp. 1894-1899 ◽  
Author(s):  
J D Young ◽  
W R Clark ◽  
C C Liu ◽  
Z A Cohn
Keyword(s):  
Gradient Centrifugation ◽  
Cell Types ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Cellular Targets ◽  
Calcium Dependent ◽  
The Past ◽  
Complex Picture ◽  
Density Band ◽  
Dependent Pathway

Cytotoxic T lymphocytes have been thought to lyse cellular targets in the past by a calcium-dependent pathway. This notion was recently supported by the identification and purification of a pore-forming protein (perforin) from the granules of these cell types. Here, we show that perforin is absent from a number of cell lines that nevertheless display vigorous cytolytic activity toward target cells. The cytotoxic activity of eight murine CTL lines is completely or partially retained in the absence of calcium. The calcium-independent lytic activity is associated with two subcellular fraction peaks isolated by Percoll gradient centrifugation, e.g., a heavy density band migrating with granule markers and a lighter band corresponding to free cytosolic material. These results suggest a complex picture of lymphocyte-mediated killing involving probably multiple mechanisms and mediators that may operate in concert or independently in the delivery of the lethal hit.

Mistargeting of Normal Cells in Anti-CD30 Immunotherapy of Lymphoma Cells Is Blocked by Selective Metalloproteinase Inhibitor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2518-2518
Author(s):  
Vijaya L. Simhadri ◽  
Elke Pogge von Strandmann ◽  
Dennis A. Eichenhauer ◽  
Andreas Ludwig ◽  
Katrin S. Reiners ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Line ◽  
Hodgkin Lymphoma ◽  
Large Cell ◽  
Target Antigen ◽  
Target Cells ◽  
Normal Cells ◽  
Calcium Dependent ◽  
Anaplastic Lymphoma ◽  
Hodgkin Lymphoma Cell

Abstract CD30 is a transmembrane receptor which is selectively overexpressed on Hodgkin lymphoma and large cell anaplastic lymphoma and therefore an interesting target for antibody-based immunotherapy. However, the receptor is cleaved by metalloproteinases and the ectodomain is released in the environment where it competes with the CD30-based immunotherapy. Moreover, therapeutic anti-CD30 antibodies stimulate this cleavage which results in a loss of target antigen and an enhanced release of the soluble ectodomain (sCD30). In order to improve immunotherapy, we analyzed the mechanism of the release and the function of resulting sCD30. By means of FACS analysis, we demonstrate that sCD30, like membrane-anchored CD30, binds to CD30 ligand (CD153)-expressing cells. Since monoclonal antibodies bind to both CD30 and sCD30, this results in unwanted targeting of these “non-target” cells via sCD30 bridging. To overcome the damage of normal cells in immunotherapy as a consequence of sCD30-binding, we analyzed the mechanism involved in the release of sCD30. Shedding of CD30 can be enhanced by PKC activation involving the disintegrin metalloproteinase ADAM17 but not free cytoplasmic calcium. In contrast, antibody-induced CD30 shedding is calcium-dependent and PKC-independent. Using the ADAM10 inhibitor GI254023X and a ADAM10-deficient cell line generated from embryonically lethal ADAM10−/−mouse we demonstrate that antibody-mediated shedding involves the related metalloproteinase ADAM10. In co-culture experiments, the antibody-induced transfer of sCD30 from the Hodgkin lymphoma cell line L540 to the CD30-negative but CD153-expressing mast cell line HMC-1 was inhibited by GI254023X. These findings suggest that selective metalloproteinase inhibitors blocking antibody-induced shedding of target antigens could be of therapeutic value to increase the specificity and reduce side-effects of immunotherapy with monoclonal antibodies.

Ultrastructural Changes in Tumor Cells During Human Peripheral Blood Monocyte-Mediated Cytotoxicity

1981 ◽  
Vol 39 ◽  
pp. 452-453
Author(s):  
K. E. Muse ◽  
D. G. Fischer ◽  
H. S. Koren
Keyword(s):  
Target Cell ◽  
Human Peripheral Blood ◽  
Mononuclear Phagocytes ◽  
Ultrastructural Changes ◽  
Target Cells ◽  
Limited Information ◽  
Blood Monocytes ◽  
Tumoricidal Activity ◽  
Activated State

Mononuclear phagocytes, a pluripotential cell line, manifest an array of basic extracellular functions. Among these physiological regulatory functions is the expression of spontaneous cytolytic potential against tumor cell targets.The limited observations on human cells, almost exclusively blood monocytes, initially reported limited or a lack of tumoricidal activity in the absence of antibody. More recently, freshly obtained monocytes have been reported to spontaneously impair the biability of tumor target cells in vitro (Harowitz et al., 1979; Montavani et al., 1979; Hammerstrom, 1979). Although the mechanism by which effector cells express cytotoxicity is poorly understood, discrete steps can be distinguished in the process of cell mediated cytotoxicity: recognition and binding of effector to target cells,a lethal-hit stage, and subsequent lysis of the target cell. Other important parameters in monocyte-mediated cytotoxicity include, activated state of the monocyte, effector cell concentrations, and target cell suseptibility. However, limited information is available with regard to the ultrastructural changes accompanying monocyte-mediated cytotoxicity.

The Effect of Androgen Depletion and Replacement on the Epithelium of the Seminal Vesicle of the Aging Rat

1975 ◽  
Vol 33 ◽  
pp. 590-591
Author(s):  
Venita F. Allison
Keyword(s):  
Cell Proliferation ◽  
Seminal Vesicle ◽  
Male Rats ◽  
Target Cells ◽  
Cell Regeneration ◽  
Secretory Function ◽  
Electron Microscopic ◽  
Aging Rat ◽  
Microscopic Studies ◽  
Androgen Depletion

In 1930, Moore, Hughes and Gallager reported that after castration seminal vesicle epithelial cell atrophy occurred and that cell regeneration could be achieved with daily injections of testis extract. Electron microscopic studies have confirmed those observations and have shown that testosterone injections restore the epithelium of the seminal vesicle in adult castrated male rats. Studies concerned with the metabolism of androgens point out that dihydrotestosterone stimulates cell proliferation and that other metabolites of testosterone probably influence secretory function in certain target cells.Although the influence of androgens on adult seminal vesicle epithelial cytology is well documented, little is known of the effect of androgen depletion and replacement on those cells in aging animals. The present study is concerned with the effect of castration and testosterone injection on the epithelium of the seminal vesicle of aging rats.

Reduction of Potassium in Kidney Proximal Tubules to Aid in Electron Probe X-Ray Microanalysis of Calcium

1985 ◽  
Vol 43 ◽  
pp. 474-475
Author(s):  
A. LeFurgey ◽  
P. Ingram ◽  
L.J. Mandel
Keyword(s):  
Smooth Muscle ◽  
Proximal Tubule ◽  
Electron Probe ◽  
Clinical Applications ◽  
Proximal Tubules ◽  
Rabbit Kidney ◽  
Target Cells ◽  
X Ray ◽  
Freeze Dried

For quantitative determination of subcellular Ca distribution by electron probe x-ray microanalysis, decreasing (and/or eliminating) the K content of the cell maximizes the ability to accurately separate the overlapping K Kß and Ca Kα peaks in the x-ray spectra. For example, rubidium has been effectively substituted for potassium in smooth muscle cells, thus giving an improvement in calcium measurements. Ouabain, a cardiac glycoside widely used in experimental and clinical applications, inhibits Na-K ATPase at the cell membrane and thus alters the cytoplasmic ion (Na,K) content of target cells. In epithelial cells primarily involved in active transport, such as the proximal tubule of the rabbit kidney, ouabain rapidly (t1/2= 2 mins) causes a decrease2 in intracellular K, but does not change intracellular total or free Ca for up to 30 mins. In the present study we have taken advantage of this effect of ouabain to determine the mitochondrial and cytoplasmic Ca content in freeze-dried cryosections of kidney proximal tubule by electron probe x-ray microanalysis.

The effects of Cyclosporin-A (CYA) on the Ultrastructure of Gingival Mast Cells (GMC) in Behcet's disease (BD)

1990 ◽  
Vol 48 (3) ◽  
pp. 358-359
Author(s):  
Oktay Arda ◽  
Ulkü Noyan ◽  
Selgçk Yilmaz ◽  
Mustafa Taşyürekli ◽  
İsmail Seçkin ◽  
...  
Keyword(s):  
Unknown Etiology ◽  
Control Group ◽  
Target Cells ◽  
Gingival Hyperplasia ◽  
Cellular Activity ◽  
Direct Relation ◽  
Immune Disease ◽  
Genital Ulceration ◽  
Functional Changes ◽  
The Third

Turkish dermatologist, H. Beheet described the disease as recurrent triad of iritis, oral aphthous lesions and genital ulceration. Auto immune disease is the recent focus on the unknown etiology which is still being discussed. Among the other immunosupressive drugs, CyA included in it's treatment newly. One of the important side effects of this drug is gingival hyperplasia which has a direct relation with the presence of teeth and periodontal tissue. We are interested in the ultrastructure of immunocompetent target cells that were affected by CyA in BD.Three groups arranged in each having 5 patients with BD. Control group was the first and didn’t have CyA treatment. Patients who had CyA, but didn’t show gingival hyperplasia assembled the second group. The ones displaying gingival hyperplasia following CyA therapy formed the third group. GMC of control group and their granules are shown in FIG. 1,2,3. GMC of the second group presented initiation of supplementary cellular activity and possible maturing functional changes with the signs of increased number of mitochondria and accumulation of numerous dense cored granules next to few normal ones, FIG. 4,5,6.

Plant peptide hormone signalling

2015 ◽  
Vol 58 ◽  
pp. 115-131 ◽  
Author(s):  
Ayane Motomitsu ◽  
Shinichiro Sawa ◽  
Takashi Ishida
Keyword(s):  
Communication Systems ◽  
Cell Communication ◽  
Peptide Hormone ◽  
Peptide Hormones ◽  
Target Cells ◽  
Signalling Molecules ◽  
Receptor Complexes ◽  
Environmental Responses ◽  
Plant Life Cycle ◽  
Multicellular Organisms

The ligand–receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone–receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.

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