Tumor necrosis factor triggers redistribution to a Triton X-100-insoluble, cytoskeletal fraction of β2 integrins, NADPH oxidase components, tyrosine phosphorylated proteins, and the protein tyrosine kinase p58<i>fgr</i> in human neutrophils adherent to fibrinogen

Yan, Sen; Fumagalli, Laura; Dusi, Stefano; Berton, Giorgio

doi:10.1002/jlb.58.5.595

Cited by 60 publications

(48 citation statements)

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“…Mac-1 is linked to the actin cytoskeleton, which is proposed to act as a "platform" to bring signal transduction proteins in close proximity to various surface receptors (including integrins). 20,21,[54][55][56] We observed partial colocalization of Mac-1 with Fc␣RI on human PMNs on Fc␣RI crosslinking, which may represent the immobile (cytoskeletonassociated) population of Mac-1 (data not shown). All our experiments were performed in the absence of serum complement to exclude complement-mediated cytotoxicity.…”

Section: Mac-1 In Fcr-mediated Cytotoxicity 2483mentioning

confidence: 86%

Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation

Spriel

Leusen

Egmond

et al. 2001

Blood

188

172

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IntroductionAntibodies have been studied extensively for their use in immunotherapy of cancer. [1][2][3][4] It is evident that receptors for the Fc portion of immunoglobulins (FcRs) on myeloid cells are critical in triggering antitumor cytotoxicity in vivo. 5,6 Antibody-dependent cellular cytotoxicity (ADCC), considered crucial for antibody-mediated tumor cell degradation, can be mediated by polymorphonuclear leukocytes (PMNs), monocytes/macrophages, eosinophils, and natural killer (NK) cells. 7,8 These effector cells use different cytotoxic mechanisms, depending on their activation state and the nature of the target. 7,9-12 PMNs, representing the most populous type of white blood cell, exhibit fast recruitment activity in vivo. Potent and very rapid (within 30 minutes) PMN cytotoxicity toward various tumor targets has been documented. 10,[13][14][15] Two classes of immunoglobulin (Ig)G receptors (Fc␥RIIa, CD32, and Fc␥RIIIb, CD16) and one class of IgA receptor (Fc␣RI, CD89) have been identified on human PMNs, whereas Fc␥RI (CD64) expression is inducible on PMNs on stimulation with granulocyte colony-stimulating factor. 16 PMNs can trigger ADCC by engagement of Fc␥RI, Fc␥RIIa, and Fc␣RI. Fc␣RI, however, has been observed to be the most effective FcR for PMN-mediated tumor cell killing. 14,17 Mac-1 (CR3, CD11b/CD18) is a member of the ␤ 2 integrin family, which includes Mac-1, LFA-1 (CD11a/CD18), and gp150/95 (CR4, CD11c/CD18). 18,19 These receptors, sharing a common ␤-chain (CD18), can bind multiple ligands and can regulate various leukocyte functions. Mac-1 represents the predominant ␤ 2 integrin on PMNs and is furthermore expressed on monocytes/macrophages and NK cells. Several PMN functions are regulated by Mac-1, including adhesion, migration, chemotaxis, phagocytosis, respiratory burst activity, and degranulation. 18 On activation, Mac-1 is able to initiate signaling by its linkage to the actin cytoskeleton and associated signaling proteins. 20,21 A number of studies described Mac-1 cooperation with different receptors on PMNs, indicating Mac-1 to be a signaling partner for other receptors. 22 These include FMLP receptors, LPS/LBP receptors (CD14), urokinase plasminogen activator receptor (CD87), and Fc receptors. [22][23][24][25][26] Mac-1 was found to trigger Ab-dependent phagocytosis by Fc␥RIIIb in fibroblasts transfected with both Mac-1 and Fc␥RIIIb, whereas cells expressing only Mac-1 or Fc␥RIIIb were unable to ingest Ab-opsonized particles. 27 Mac-1 cooperation with Fc␥RIIIb in the generation of PMN respiratory burst has been described as well. 28 Furthermore, Mac-1 restored IgG-dependent phagocytosis of transfectants with Fc␥RIIa tail-minus mutants. 29 Importantly, PMNs from patients with leukocyte adhesion deficiency, who lack CD18, were shown to be severely impaired in mediating phagocytosis and ADCC. 18,[30][31][32] Although the relative contribution of individual ␤ 2 integrins remains to be determined, various studies point to an important role of Mac-1 in FcR-mediated cytotoxicity. Targets st...

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Section: Mac-1 In Fcr-mediated Cytotoxicity 2483mentioning

confidence: 86%

Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation

Spriel

Leusen

Egmond

et al. 2001

Blood

188

172

View full text Add to dashboard Cite

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“…Accumulating evidence supports a link between the actin cytoskeleton and actin-binding proteins in the activation of phagocytic and non-phagocytic NADPH oxidase (23)(24)(25)(26)(27). Stimulation of neutrophils with phorbol ester induces translocation of p47 phox to the cytoskeleton without altering the distribution of either p40 phox or p67 phox and increases the oxidase activity that co-sediments with a heavy plasma membrane fraction consisting of actin and fodrin (28,29).…”

Section: Discussionmentioning

confidence: 98%

“…Actin cytoskeleton and other cytoskeletal proteins may play a role in phagocytic and non-phagocytic assembly and the activation of NADPH oxidase (23)(24)(25)(26)(27). In phorbol ester-stimulated neutrophils, oxidase activity has been shown to co-sediment with the heavy plasma membrane fraction that contains actin and fodrin; furthermore, the labile oxidase can be stabilized by chemical cross-linking and is not extractable by Triton X-100, suggesting that an interaction occurs between the NADPH oxidase complex and actin filaments (28,29).…”

mentioning

confidence: 99%

Regulation of Hyperoxia-induced NADPH Oxidase Activation in Human Lung Endothelial Cells by the Actin Cytoskeleton and Cortactin

Usatyuk

Romer

et al. 2007

Journal of Biological Chemistry

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Although the actin cytoskeleton has been implicated in the control of NADPH oxidase in phagocytosis, very little is known about the cytoskeletal regulation of endothelial NADPH oxidase assembly and activation. Here, we report a role for cortactin and the tyrosine phosphorylation of cortactin in hyperoxiainduced NADPH oxidase activation and ROS production in human pulmonary artery ECs (HPAECs). Exposure of HPAECs to hyperoxia for 3 h induced NADPH oxidase activation, as demonstrated by enhanced superoxide production. Hyperoxia also caused a thickening of the subcortical dense peripheral F-actin band and increased the localization of cortactin in the cortical regions and lamellipodia at cell-cell borders that protruded under neighboring cells. Pretreatment of HPAECs with the actin-stabilizing agent phallacidin attenuated hyperoxia-induced cortical actin thickening and ROS production, whereas cytochalasin D and latrunculin A enhanced basal and hyperoxia-induced ROS formation. In HPAECs, a 3-h hyperoxic exposure enhanced the tyrosine phosphorylation of cortactin and interaction between cortactin and p47 phox , a subcomponent of the EC NADPH oxidase, when compared with normoxic cells. Furthermore, transfection of HPAECs with cortactin small interfering RNA or myristoylated cortactin Src homology domain 3 blocking peptide attenuated ROS production and the hyperoxia-induced translocation of p47 phox to the cell periphery. Similarly, down-regulation of Src with Src small interfering RNA attenuated the hyperoxia-mediated phosphorylation of cortactin tyrosines and blocked the association of cortactin with actin and p47phox . In addition, the hyperoxia-induced generation of ROS was significantly lower in ECs expressing a tyrosine-deficient mutant of cortactin than in vector control or wild-type cells. These data demonstrate a novel function for cortactin and actin in hyperoxiainduced activation of NADPH oxidase and ROS generation in human lung endothelial cells. production that is dependent on NADPH oxidase activation and independent of the mitochondrial electron transport or xanthine/xanthine oxidase systems (10). The mechanisms of NADPH oxidase activation are complex. In phagocytes, activation of NADPH oxidase requires serine phosphorylation of the cytosolic p47 phox , p67 phox , and p40 phox components, assembly of the phosphorylated subunits with Rac2, and translocation to the phagosomes for association with cytochrome b 558. Here, one-electron reduction of molecular O 2 to O 2 . occurs with NADPH as the electron donor (7). In leukocytes, formyl-Met-Leu-Phe-OH or phorbol ester stimulates phosphorylation of p47 phox at multiple serine residues through reactions involving several protein kinases such as protein kinase C, protein kinase A, and mitogen-activated protein kinases (14 -17). In HPAECs, tumor necrosis factor-␣-medi-*This work was supported by National Institutes of Health Grants RO1 HL 69909 (to V. N.), PO1 HL 58064 (to V. N. and J. G. N. G.) and DE13079-01 and AI061042 (to L. H. R.). The costs of publication...

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“…130 The same signals induce the association of b2-integrins, NADPH-oxidase components, and FcgRII with the cytoskeleton, the latter being increased in the presence of anti-PR3 or anti-MPO antibodies. 16,131 Upon TNF-a priming, PR3 forms a complex with NB1 and with CD11b/CD18, all three proteins being localized in cholesterol-rich domains (lipid rafts), 60,132 together with signaling molecules, cross-linked FcgRII, 133,134 and NADPH-oxidase membrane components. 135 to specifically trigger degranulation and extracellular release of superoxide from the CD177 + neutrophil subset by a mechanism involving b2-integrins.…”

Section: Consequences Of the Biphasic Expression Of Membrane Pr3mentioning

confidence: 99%

Endothelium-Neutrophil Interactions in ANCA-Associated Diseases

Halbwachs

Lesavre

2012

Journal of the American Society of Nephrology

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The two salient features of ANCA-associated vasculitis (AAV) are the restricted microvessel localization and the mechanism of inflammatory damage, independent of vascular immune deposits. The microvessel localization of the disease is due to the ANCA antigen accessibility, which is restricted to the membrane of neutrophils engaged in b2-integrin-mediated adhesion, while these antigens are cytoplasmic and inaccessible in resting neutrophils. The inflammatory vascular damage is the consequence of maximal proinflammatory responses of neutrophils, which face cumulative stimulations by TNF-a, b2-integrin engagement, C5a, and ANCA by the FcgRII receptor. This results in the premature intravascular explosive release by adherent neutrophils of all of their available weapons, normally designed to kill IgG-opsonized bacteria after migration in infected tissues.

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Tumor necrosis factor triggers redistribution to a Triton X-100-insoluble, cytoskeletal fraction of β2 integrins, NADPH oxidase components, tyrosine phosphorylated proteins, and the protein tyrosine kinase p58fgr in human neutrophils adherent to fibrinogen

Cited by 60 publications

References 0 publications

Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation

Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation

Regulation of Hyperoxia-induced NADPH Oxidase Activation in Human Lung Endothelial Cells by the Actin Cytoskeleton and Cortactin

Endothelium-Neutrophil Interactions in ANCA-Associated Diseases

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