Calmodulin: Effects of cell stimuli and drugs on cellular activation

Author(s):  
Margaret E. Gnegy
Keyword(s):  
2004 ◽  
Vol 287 (1) ◽  
pp. L210-L216 ◽  
Author(s):  
Dirk Haufe ◽  
Thomas Luther ◽  
Matthias Kotzsch ◽  
Lilla Knels ◽  
Thea Koch

Intrapulmonary application of perfluorocarbons (PFC) in acute lung injury is associated with anti-inflammatory effects. A direct impact on leukocytic function may be involved. To further elucidate PFC effects on cellular activation, we compared in an in vitro model the response of concanavalin A (ConA)-stimulated lymphocytes and monocytes exposed to perfluorohexane. We hypothesized that perfluorohexane attenuates the action of the lectin ConA by altering stimulant-receptor interaction on the cell surface. Mononuclear blood cells were stimulated by incubation with ConA in the presence of different amounts of perfluorohexane. The response of lymphocytes and monocytes was determined by means of IL-2 secretion and tissue factor (TF) expression, respectively. The influence of perfluorohexane on cell-surface binding of fluorescence-labeled ConA was studied using flow cytofluorometry and fluorescence microscopy. Perfluorohexane itself did not induce a cellular activation but significantly inhibited both monocytic TF expression and, to a far greater extent, IL-2 secretion of ConA-stimulated mononuclear blood cells. The effect of perfluorohexane was due neither to an alteration of cell viability nor to a binding of the stimulant. The amount of cell surface-bound ConA was not altered by perfluorohexane, and the overall pattern of ConA receptor rearrangement did not differ between controls and treated cells. In the present study, we provide further evidence for an anti-inflammatory effect of PFC that might be beneficial in states of pulmonary hyperinflammation. A PFC-induced alteration of stimulant-receptor interaction on the surface membrane does not seem to be the cause of attenuated cell activation.


2002 ◽  
Vol 115 (12) ◽  
pp. 2603-2611 ◽  
Author(s):  
Martha Triantafilou ◽  
Kensuke Miyake ◽  
Douglas T. Golenbock ◽  
Kathy Triantafilou

The plasma membrane of cells is composed of lateral heterogeneities,patches and microdomains. These membrane microdomains or lipid rafts are enriched in glycosphingolipids and cholesterol and have been implicated in cellular processes such as membrane sorting and signal transduction. In this study we investigated the importance of lipid raft formation in the innate immune recognition of bacteria using biochemical and fluorescence imaging techniques. We found that receptor molecules that are implicated in lipopolysaccharide (LPS)-cellular activation, such as CD14, heat shock protein(hsp) 70, 90, Chemokine receptor 4 (CXCR4), growth differentiation factor 5(GDF5) and Toll-like receptor 4 (TLR4), are present in microdomains following LPS stimulation. Lipid raft integrity is essential for LPS-cellular activation, since raft-disrupting drugs, such as nystatin or MCD, inhibit LPS-induced TNF-α secretion. Our results suggest that the entire bacterial recognition system is based around the ligation of CD14 by bacterial components and the recruitment of multiple signalling molecules, such as hsp70, hsp90, CXCR4, GDF5 and TLR4, at the site of CD14-LPS ligation, within the lipid rafts.


2005 ◽  
Vol 94 (11) ◽  
pp. 1004-1011 ◽  
Author(s):  
Frédéric Adam ◽  
Shilun Zheng ◽  
Nilesh Joshi ◽  
David Kelton ◽  
Amin Sandhu ◽  
...  

SummaryMultimerin 1 (MMRN1) is a large, soluble, polymeric, factor V binding protein and member of the EMILIN protein family.In vivo, MMRN1 is found in platelets, megakaryocytes, endothelium and extracellular matrix fibers, but not in plasma. To address the mechanism of MMRN1 binding to activated platelets and endothelial cells, we investigated the identity of the major MMRN1 receptors on these cells using wild-type and RGE-forms of recombinant MMRN1. Ligand capture, cell adhesion, ELISA and flow cytometry analyses of platelet-MMRN1 binding, indicated that MMRN1 binds to integrins αIIbβ3 and αvβ3. Endothelial cell binding to MMRN1 was predominantly mediated by αvβ3 and did not require the MMRN1 RGD site or cellular activation. Like many other αvβ3 ligands, MMRN1 had the ability to support adhesion of additional cell types, including stimulated neutrophils. Expression studies, using a cell line capable of endothelial-like MMRN1 processing, indicated that MMRN1 adhesion to cellular receptors enhanced its extracellular matrix fiber assembly. These studies implicate integrin-mediated binding in MMRN1 attachment to cells and indicate that MMRN1 is a ligand for αIIbβ3 and αvβ3.


2017 ◽  
Vol 48 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Nico Nitzsche ◽  
Tilo Neuendorf ◽  
Sebastian Gehlert ◽  
Michael Fröhlich ◽  
Henry Schulz

Apmis ◽  
2000 ◽  
Vol 108 (3) ◽  
pp. 201-208 ◽  
Author(s):  
Jero Calafat ◽  
Hans Janssen ◽  
Edward F. Knol ◽  
Johan Malm ◽  
Arne Egesten

2012 ◽  
Vol 23 (4) ◽  
pp. 322-327 ◽  
Author(s):  
Ruthinéia Diogénes Alves Uchoa Lins ◽  
Pollianna Muniz Alves ◽  
Gustavo Pina Godoy ◽  
Ericka Janine Dantas Silveira ◽  
Lélia Maria Guedes Queiroz ◽  
...  

It was assessed the immunohistochemical profile of CD25+ cells in cases of chronic gingivitis (CG) and chronic periodontitis (CP). Immunohistochemistry was carried out using streptoavidin-biotin complex and anti-CD25 antibody in 17 cases of CG and 25 cases of CP. Sixteen cases (94.1%) of CG were immunopositive. CD25 was focally expressed in 50% of the sample and diffusely expressed in 25%. The stained cells were localized not only beneath the epithelium, but also far from it. In relation to the cellular density quantification of CD25+ cells, score ++ was the most common. Concerning CP, all cases were immunopositive. CD25+ cells were expressed in focal or diffuse pattern either close or far from the epithelium. Diffuse distribution of positive cells throughout the connective tissue was seen in 60% of the cases and 32% showed focal or diffuse cellular pattern. Sixteen cases (64%) received score +++. It was identified that CD25+ cells are present in either a focal or a diffuse pattern in connective tissue. Significant differences in the density of cellular immunostaining between CG and CP were found. The greatest density was observed in CP cases, which suggests that the infiltrate of lymphocytes show a higher degree of cellular activation in periodontitis compared with gingivitis.


1997 ◽  
Vol 90 (5) ◽  
pp. 531-534 ◽  
Author(s):  
RANI SHARMA ◽  
BETTY HERNDON ◽  
MICHELLE DEW ◽  
UTE ROSA

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