共查询到20条相似文献,搜索用时 9 毫秒
1.
Dib K Melander F Axelsson L Dagher MC Aspenström P Andersson T 《The Journal of biological chemistry》2003,278(26):24181-24188
In human neutrophils, beta2 integrin engagement mediated a decrease in GTP-bound Rac1 and Rac2. Pretreatment of neutrophils with LY294002 or PP1 (inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) and Src kinases, respectively) partly reversed the beta2 integrin-induced down-regulation of Rac activities. In contrast, beta2 integrins induced stimulation of Cdc42 that was independent of Src family members. The PI 3-kinase dependence of the beta2 integrin-mediated decrease in GTP-bound Rac could be explained by an enhanced Rac-GAP activity, since this activity was blocked by LY204002, whereas PP1 only had a minor effect. The fact that only Rac1 but not Rac2 (the dominating Rac) redistributed to the detergent-insoluble fraction and that it was independent of GTP loading excludes the possibility that down-regulation of Rac activities was due to depletion of GTP-bound Rac from the detergent-soluble fraction. The beta2 integrin-triggered relocalization of Rac1 to the cytoskeleton was enabled by a PI 3-kinase-induced dissociation of Rac1 from LyGDI. The dissociations of Rac1 and Rac2 from LyGDI also explained the PI 3-kinase-dependent translocations of Rac GTPases to the plasma membrane. However, these accumulations of Rac in the membrane, as well as that of p47phox and p67phox, were also regulated by Src tyrosine kinases. Inasmuch as Rac GTPases are part of the NADPH oxidase and the respiratory burst is elicited in neutrophils adherent by beta2 integrins, our results indicate that activation of the NADPH oxidase does not depend on the levels of Rac-GTP but instead requires a beta2 integrin-induced targeting of the Rac GTPases as well as p47phox and p67phox to the plasma membrane. 相似文献
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Cell adhesion to extracellular matrix components involves integrin binding, receptor clustering, and recruitment of cytoskeletal elements, leading to the formation of discrete adhesive structures (focal adhesions). A force balance, macroscopic-to-microscopic model of these adhesive events is presented in the context of experimentally measured parameters. Integrin bond force, bond numbers, and distribution along the contact area strongly modulated the resulting adhesive force. Furthermore, focal adhesion assembly enhanced adhesion strength by 30% over integrin clustering alone. Predicted values are in excellent agreement with experimental results. This model provides a simple framework to systematically analyze the contributions of different adhesive parameters to overall adhesion strength. 相似文献
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Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion 总被引:11,自引:0,他引:11
Xie B Zhao J Kitagawa M Durbin J Madri JA Guan JL Fu XY 《The Journal of biological chemistry》2001,276(22):19512-19523
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Phyoe Kyawe Myint Atsushi Ito Michael G. Appiah Gideon Obeng Samuel Darkwah Eiji Kawamoto Arong Gaowa Eun Jeong Park Motomu Shimaoka 《Biochemistry and Biophysics Reports》2021
Irisin, a myokine released from skeletal muscle, has recently been found to act as a ligand for the integrins αVβ5, αVβ1, and α5β1 expressed on mesenchymal cells, thereby playing an important role in the metabolic remodeling of the bone, skeletal muscle and adipose tissues. Although the immune-modulatory effects of irisin in chronic inflammation have been documented, its interactions with lymphocytic integrins have yet to be elucidated. Here, we show that irisin supports the cell adhesion of human and mouse lymphocytes. Cell adhesion assays using a panel of inhibitory antibodies to integrins have shown that irisin-mediated lymphocyte adhesion involves multiple integrins including not only α4β1 and α5β1, but also leukocyte-specific αLβ2 and α4β7. Importantly, mouse lymphocytic TK-1 cells that lack the expression of β1 integrins have exhibited αLβ2- and α4β7-mediated cell adhesion to irisin. Irisin has also been demonstrated to bind to purified recombinant integrin αLβ2 and α4β7 proteins. Thus, irisin represents a novel ligand for integrin αLβ2 and α4β7, capable of supporting lymphocyte cell adhesion independently of β1 integrins. These results suggest that irisin may play an important role in regulating lymphocyte adhesion and migration in the inflamed vasculature. 相似文献
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Integrins are the major family of cell adhesion receptors that mediate cell adhesion to the extracellular matrix (ECM). Integrin-mediated adhesion and signaling play essential roles in neural development. In this study, we have used echistatin, an RGD-containing short monomeric disintegrin, to investigate the role of integrin-mediated adhesion and signaling during retinal development in Xenopus. Application of echistatin to Xenopus retinal-derived XR1 glial cells inhibited the three stages of integrin-mediated adhesion: cell attachment, cell spreading, and formation of focal adhesions and stress fibers. XR1 cell attachment and spreading increased tyrosine phosphorylation of paxillin, a focal adhesion associated protein, while echistatin significantly decreased phosphorylation levels of paxillin. Application of echistatin or beta(1) integrin function blocking antibody to the embryonic Xenopus retina disrupted retinal lamination and produced rosette structures with ectopic photoreceptors in the outer retina. These results indicate that integrin-mediated cell-ECM interactions play a critical role in cell adhesion, migration, and morphogenesis during vertebrate retinal development. 相似文献
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P. Bellavite S. Chirumbolo G. Lippi G. Andrioli L. Bonazzi I. Ferro 《Cell biochemistry and function》1993,11(4):231-239
Neutrophils, treated with sequential additions of bacterial products such as endotoxin (E. Coli lipopolysaccharide, LPS) and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), undergo to metabolic activation and express membrane-anchoring proteins that promote adhesion to serum-coated culture wells. By investigating the dose–response relationships of these phenomena, we have found that: (a) resting neutrophils do not produce a significant amount of superoxide (O) and show only minimal adhesion to serum-coated plastic surfaces; (b) fully activatory doeses (> 5 × 10?8 M ) of fMLP induce the release of O and a significant increase of the cell adhesion; (c) pretreatment of the cells for 1 h with LPS augments cell adhesion to serum-coated culture wells in the absence of further stimulation and primes the neutrophils to enhanced fMLP-dependent O release; (d) addition of low, substimulatory doses of fMLP (from 10?10 M to 5 × 10?9 M ) inhibits and reverses the adhesion of LPS-treated cells, (e) high fMLP doses (> 10?7 M ) are additive to LPS in promoting adhesion. Phorbol-myristate acetate (> 10?9M) increased adhesion in both normal and LPS-treated neutrophils, but low doses of this stimulant did not inhibit adhesion. Low doses (10?9 M ) of fMLP increased intracellular cyclic AMP in both normal and LPS-treated neutrophils, suggesting that stimulus-induced rises in cAMP may be the negative signal responsible for down-modulation of adhesion. Low (5 × 10?9 M ) and high (5 × 10?7 M ) fMLP doses induced the same increase of expression of CD11/CD18 integrins, indicating that the inhibition of adhesion caused by low doses is not due to quantitative down-regulation of integrins. These findings may provide an in vitro model of the complex biological events involved in the regulation of neutrophil adhesion. 相似文献
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Fiaschi T Cozzi G Raugei G Formigli L Ramponi G Chiarugi P 《The Journal of biological chemistry》2006,281(32):22983-22991
Redox sensitivity of actin toward an exogenous oxidative stress has recently been reported. We report here the first evidence of in vivo actin redox regulation by a physiological source of reactive oxygen species, specifically those species generated by integrin receptors during cell adhesion. Actin oxidation takes place via the formation of a mixed disulfide between cysteine 374 and glutathione; this modification is essential for spreading and for cytoskeleton organization. Impairment of actin glutathionylation, either through GSH depletion or expression of the C374A redox-insensitive mutant, greatly affects cell spreading and the formation of stress fibers, leading to inhibition of the disassembly of the actinomyosin complex. These data suggest that actin glutathionylation is essential for cell spreading and cytoskeleton organization and that it plays a key role in disassembly of actinomyosin complex during cell adhesion. 相似文献
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Marine endotherms in the polar regions face a formidable thermal challenge when swimming in cold water. Hence, they use morphological (fat, blubber) adjustment and peripheral vasoconstriction to reduce demands for heat production in water. The animals then regain normothermia when resting ashore. In the king penguin (Aptenodytes patagonicus) metabolic rate is lower in fed than in fasted individuals during subsequent rewarming on land. This has been suggested to be a consequence of diversion of blood flow to the splanchnic region in fed birds, which reduces peripheral temperatures. However, peripheral temperatures during recovery have never been investigated in birds with different nutritional status. The aim of this study was, therefore, to measure subcutaneous and abdominal temperatures during the rewarming phase on land in fasted and fed king penguins, and investigate to which extent any different rewarming were reflected in recovery metabolic rate (MRR) after long term immersion in cold water. We hypothesized that fed individuals would have a slower increase of subcutaneous temperatures compared to fasted penguins, and a correspondingly lower MRR. Subcutaneous tissues reached normothermia after 24.15 (back) and 21.36 min (flank), which was twice as fast as in the abdomen (46.82 min). However, recovery time was not affected by nutritional condition. MRR during global rewarming (4.56 ± 0.42 W kg−1) was twice as high as resting metabolic rate (RMR; 2.16 ± 0.59 W kg−1). However, MRR was not dependent on feeding status and was significantly elevated above RMR only until subcutaneous temperature had recovered. Contrary to our prediction, fed individuals did not reduce the subcutaneous circulation compared to fasted penguins and did not show any changes in MRR during subsequent recovery. It seems likely that lower metabolic rate in fed king penguins on land reported in other studies might not have been caused primarily by increased circulation to the visceral organs. 相似文献
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Changes in ascorbate levels on stimulation of human neutrophils 总被引:1,自引:0,他引:1
Changes in ascorbate levels have been measured in human neutrophils stimulated with opsonized zymosan, phorbol myristate acetate and formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe), in the presence and absence of cytochalasin B. After stimulation with opsonized zymosan or phorbol myristate acetate, there was no loss of total ascorbate, but 30-40% of the reduced ascorbate was oxidized to dehydroascorbate. Superoxide dismutase and catalase added to the cell suspension did not inhibit this oxidation. fMet-Leu-Phe, however, gave no net oxidation but about 20% of the total ascorbate was lost during 2 h incubation. These results imply that there is not a simple relationship between superoxide and hydrogen peroxide production and ascorbate oxidation, and that release of ascorbate into the phagolysosomes does not occur. 相似文献
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A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling 总被引:21,自引:0,他引:21
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The assembly of signaling molecules surrounding the integrin family of adhesion receptors remains poorly understood. Recently, the membrane protein caveolin was found in complexes with beta1 integrins. Caveolin binds cholesterol and several signaling molecules potentially linked to integrin function, e.g., Src family kinases, although caveolin has not been directly implicated in integrin-dependent adhesion. Here we report that depletion of caveolin by antisense methodology in kidney 293 cells disrupts the association of Src kinases with beta1 integrins resulting in loss of focal adhesion sites, ligand-induced focal adhesion kinase (FAK) phosphorylation, and adhesion. The nonintegrin urokinase receptor (uPAR) associates with and stabilizes beta1 integrin/caveolin complexes. Depletion of caveolin in uPAR-expressing 293 cells also disrupts uPAR/integrin complexes and uPAR-dependent adhesion. Further, beta1 integrin/caveolin complexes could be disassociated by uPAR-binding peptides in both uPAR-transfected 293 cells and human vascular smooth muscle cells. Disruption of complexes by peptides in intact smooth muscle cells blocks the association of Src family kinases with beta1 integrins and markedly impairs their migration on fibronectin. We conclude that ligand-induced signaling necessary for normal beta1 integrin function requires caveolin and is regulated by uPAR. Caveolin and uPAR may operate within adhesion sites to organize kinase-rich lipid domains in proximity to integrins, promoting efficient signal transduction. 相似文献
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Kevin Luftman 《Biochemical and biophysical research communications》2009,380(1):65-36761
Integrins are transmembrane receptors for cell adhesion to the extracellular matrix. In cell migration, integrins are endocytosed from the plasma membrane or the cell surface, transported in vesicles and exocytosed actively at the cell front. In the present study, we examined the roles of VAMP3, a SNARE protein that mediates exocytosis, in cell migration and integrin trafficking. Small interfering RNA (siRNA)-induced silencing of VAMP3 inhibited chemotactic cell migration by more than 60% without affecting cell proliferation. VAMP3 silencing reduced the levels of β1 integrin at the cell surface but had no effect on total cellular β1 integrin, indicating that VAMP3 is required for trafficking of β1 integrin to the plasma membrane. Furthermore, VAMP3 silencing diminished cell adhesion to laminin but not to fibronectin or collagen. Taken together, these data suggest that VAMP3-dependent integrin trafficking is crucial in cell migration and cell adhesion to laminin. 相似文献
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Membrane-bound hyaluronan mediates the initial adhesive interactions between many cell types and external surfaces. In RCJ-P chondrocytes, such early contacts are mediated through a thick hyaluronidase-sensitive coat. The early adhesion is followed by integrin-mediated interactions and the formation of stable focal adhesions. During this process, the distance between the cell membrane and the surface is reduced from micrometers to few tens of nanometers. The transition from hyaluronan- to integrin-mediated adhesion was studied on glass surfaces by total internal reflection fluorescence microscopy. Hyaluronan-mediated adhesion precedes focal adhesions formation by 2-10 min. After these initial interactions, the pericellular hyaluronan remains sequestered into discrete pockets between the cell and the surface, which are a few hundreds nanometers thick and a few micrometers wide, and are flanked by focal adhesions. The hyaluronan coat facilitates the nucleation of small paxillin-rich contacts, which later mature into focal adhesions. These dynamic studies demonstrate that pericellular hyaluronan mediates initial cell-surface adhesion, and regulates the formation of focal adhesions. 相似文献
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Mandicourt G Iden S Ebnet K Aurrand-Lions M Imhof BA 《The Journal of biological chemistry》2007,282(3):1830-1837
Junctional Adhesion Molecules (JAMs) have been described as major components of tight junctions in endothelial and epithelial cells. Tight junctions are crucial for the establishment and maintenance of cell polarity. During tumor development, they are remodeled, enabling neoplastic cells to escape from constraints imposed by intercellular junctions and to adopt a migratory behavior. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of tumor cells. We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of beta1 and beta3 integrin activation. These results highlight an unexpected function for JAM-C in controlling epithelial cell conversion from a static, polarized state to a pro-migratory phenotype. 相似文献
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Cold storage of the whole liver at 4 degrees C in SBS and UW solution allowed to prevent from osmotic swelling of cells, which appeared at early stages of liver storage at 4 degrees C in just saline solutions. This effect of preserving solutions contributes to the preservation of quite high level of intracellular ATP content in liver at the first two stages of hypothermic storage (6 and 18 hrs), which preserves even during following normothermic reperfusion of an organ. A statistical ATP reduction in comparison with the control level (almost twice) can be explained on the one hand by the exhaustion of intracellular substrates of oxidation and on the other hand by their loss for the supporting of homeostasis under cold ischemia and following incubation of liver at 37 degrees C. 相似文献
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Heydtmann M Lalor PF Eksteen JA Hübscher SG Briskin M Adams DH 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(2):1055-1062
Lymphocyte recruitment to the liver is critical for viral clearance in acute hepatitis and in the pathogenesis of chronic inflammatory liver disease when persistent chronic inflammation leads to fibrosis and cirrhosis. Chemokines regulate leukocyte recruitment and positioning in tissues and are thus critical regulators of chronic inflammation. The chemokine CXCL16, which is found in liver tissue, exists in a transmembrane as well as soluble form, providing a potential mechanism for localization to particular structures. We studied the role of CXCL16 and its receptor CXCR6 in lymphocyte recruitment and retention in the liver. A higher proportion of CXCR6(+) T cells was detected in blood of hepatitis C virus patients compared with healthy subjects, and in chronic inflammatory liver disease >60% of intrahepatic T cells expressed CXCR6, including CD4, CD8, and CD56(+) T cells compared with <30% in matched blood samples. CXCR6(+) lymphocytes were found in association with CXCL16(+) bile ducts in portal tracts and with hepatocytes at sites of interface hepatitis. Analysis of CXCL16 expression and subcellular distribution in cultured human cholangiocytes, sinusoidal endothelial cells, and hepatocytes revealed that all three cell types expressed CXCL16, with the strongest staining seen on cholangiocytes. CXCL16 on the cholangiocyte membrane was able to support lymphocyte adhesion by triggering conformational activation of beta(1) integrins and binding to VCAM-1. Thus, CXCL16 can promote lymphocyte adhesion to epithelial cells and may function to attract and retain effector cells that promote biliary and hepatocyte destruction in inflammatory liver disease. 相似文献
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Whiteford JR Behrends V Kirby H Kusche-Gullberg M Muramatsu T Couchman JR 《Experimental cell research》2007,313(18):3902-3913
Syndecans are transmembrane proteoglycans that support integrin-mediated adhesion. Well documented is the contribution of syndecan-4 that interacts through its heparan sulphate chains to promote focal adhesion formation in response to fibronectin domains. This process has requirements for integrin and signaling through the cytoplasmic domain of syndecan-4. Here an alternate pathway mediated by the extracellular domains of syndecans-2 and -4 is characterized that is independent of both heparan sulphate and syndecan signaling. This pathway is restricted to mesenchymal cells and was not seen in any epithelial cell line tested, apart from vascular endothelia. The syndecan ectodomains coated as substrates promoted integrin-dependent attachment, spreading and focal adhesion formation. Syndecan-4 null cells were competent, as were fibroblasts compromised in heparan sulphate synthesis that were unable to form focal adhesions in response to fibronectin. Consistent with actin cytoskeleton organization, the process required Rho-GTP and Rho kinase. While syndecan-2 and -4 ectodomains could both promote integrin-mediated adhesion, their pathways were distinct, as shown by competition assays. Evidence for an indirect interaction of beta1 integrin with both syndecan ectodomains was obtained, all of which suggests a distinct mechanism of integrin-mediated adhesion. 相似文献
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Intracellular localization of a leukocyte adhesion glycoprotein family in the tertiary granules of human neutrophils 总被引:2,自引:0,他引:2
P Lacal R Pulido F Sánchez-Madrid C Caba?as F Mollinedo 《Biochemical and biophysical research communications》1988,154(2):641-647
Stimulation of human neutrophils by the chemoattractant formyl-methionyl-leucyl-phenylalanine or the calcium ionophore A23187 induced increments in the cell surface expression of the alpha subunits of Mo1 (CD11b) and gp150, 95 (CD11c) and their common beta subunit (CD18). These increases showed a good correlation with the extracellular release of gelatinase, a marker for tertiary granules in human neutrophils. Conversely, the cell surface expression of the alpha subunit of the lymphocyte function-associated antigen-1 or LFA-1 (CD11a) was not altered upon cell activation. By subcellular fractionation and immunoprecipitation studies, we have found that CD11b, CD11c and CD18 molecules were mainly localized in the membranes of tertiary granules, which were resolved from the specific and azurophilic granules as well as from the plasma membrane fraction. 相似文献