Differential regulation of human and murine P-selectin expression and function in vivo

Liu, Zhenghui; Miner, Jonathan J.; Yago, Tadayuki; Yao, Longbiao; Lupu, Florea; Xia, Lijun; McEver, Rodger P.

doi:10.1084/jem.20101545

Cited by 72 publications

(85 citation statements)

References 78 publications

(124 reference statements)

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“…Interestingly, P-selectin was found to be reduced in MLN4924-treated human endothelial cells following 4 h of TNF-α stimulation, although upregulation by TNF-α per se did not reach significance. This is in line with previous reports showing that human P-selectin lacks canonical NF-κB binding sites and is not up-regulated in inflammation (70,71). A preference for MLN4924 to reduce ICAM-1 and VCAM-1 but not P-selectin levels is consistent with our observation that it markedly reduced monocyte arrest on endothelium.…”

Section: /Apoesupporting

confidence: 93%

Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo

Asare

Ommer-Bläsius

Azombo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Constitutive photomorphogenesis 9 (COP9) signalosome 5 (CSN5), an isopeptidase that removes neural precursor cell-expressed, developmentally down-regulated 8 (NEDD8) moieties from cullins (thus termed "deNEDDylase") and a subunit of the cullin-RING E3 ligase-regulating COP9 signalosome complex, attenuates proinflammatory NF-κB signaling. We previously showed that CSN5 is up-regulated in human atherosclerotic arteries. Here, we investigated the role of CSN5 in atherogenesis in vivo by using mice with myeloidspecific Csn5 deletion. Genetic deletion of Csn5 in Apoe −/− mice markedly exacerbated atherosclerotic lesion formation. This was broadly observed in aortic root, arch, and total aorta of male mice, whereas the effect was less pronounced and site-specific in females. Mechanistically, Csn5 KO potentiated NF-κB signaling and proinflammatory cytokine expression in macrophages, whereas HIF-1α levels were reduced. Inversely, inhibition of NEDDylation by MLN4924 blocked proinflammatory gene expression and NF-κB activation while enhancing HIF-1α levels and the expression of M2 marker Arginase 1 in inflammatory-elicited macrophages. MLN4924 further attenuated the expression of chemokines and adhesion molecules in endothelial cells and reduced NF-κB activation and monocyte arrest on activated endothelium in vitro. In vivo, MLN4924 reduced LPS-induced inflammation, favored an antiinflammatory macrophage phenotype, and decreased the progression of early atherosclerotic lesions in mice. On the contrary, MLN4924 treatment increased neutrophil and monocyte counts in blood and had no net effect on the progression of more advanced lesions. Our data show that CSN5 is atheroprotective. We conclude that MLN4924 may be useful in preventing early atherogenesis, whereas selectively promoting CSN5-mediated deNEDDylation may be beneficial in all stages of atherosclerosis.A therosclerosis is the primary cause of cardiovascular diseases. As a chronic inflammatory condition of the vessel wall, atherosclerosis is characterized by endothelial cell activation resulting in the secretion of chemoattractant proteins such as CCL2 and macrophage migration inhibitory factor (MIF) and by increased expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These molecules synergize to sequentially recruit inflammatory cells such as monocytes and T lymphocytes into the vessel wall (1-3).The transcription factor NF-κB plays a crucial role in vascular inflammation and atherogenesis, e.g., by controlling the expression of inflammatory cytokines, chemokines, and adhesion molecules that orchestrate the recruitment and adhesion of leukocytes. Also, numerous genes that regulate differentiation, survival, and proliferation of vascular and immune cells involved in the inflammatory response are targets of NF-κB (4). In resting cells, the NF-κB dimer, p65 and p50, is inactivated by binding to the inhibitor of κB (IκB)-α protein. Inflammatory challenges such as LPS or TNF-α exposure trigg...

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Section: /Apoesupporting

confidence: 93%

Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo

Asare

Ommer-Bläsius

Azombo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…27 Murine platelet rolling on human H1326R vWF-A1 under shear flow was measured as was described for human platelets rolling on vWF-A1. 28 Membrane tethers of platelets were visualized in real-time images by differential interference contrast videomicroscopy, using a 1003 oil immersion objective lens under the indicated shear stress.…”

Section: Ex Vivo Platelet Adhesionmentioning

confidence: 99%

Platelets lacking PIP5KIγ have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion

Wang¹,

Zhao²,

Suzuki³

et al. 2013

Blood

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“…Thus, although P-selectin expression is up-regulated by tumor necrosis factor-␣ (TNF␣) and IL-1␤ in murine inflammation models, this is not the case in humans. The contributions of P/E-selectin to inflammation is thus different in murine models versus human disease (12).…”

mentioning

confidence: 98%

Silencing α1,3-Fucosyltransferases in Human Leukocytes Reveals a Role for FUT9 Enzyme during E-selectin-mediated Cell Adhesion

Buffone

Mondal

Gupta

et al. 2013

Journal of Biological Chemistry

106

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Background: During inflammation, the selectins engage glycosylated macromolecules expressed on blood leukocytes under fluid shear conditions. Results: Although all three myeloid ␣1,3-fucosyltransferases FUT9, FUT7, and FUT4 regulate human E-selectin ligand biosynthesis, FUT7 and FUT4 are sufficient to form L/P-selectin ligands. Conclusion: FUT9 plays a significant role during human, but not mouse, leukocyte-endothelial interactions. Significance: This study identifies potential ␣(1,3)FUTs regulating inflammation in humans.

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Differential regulation of human and murine P-selectin expression and function in vivo

Abstract: Basal and inducible expression of human P-selectin in transgenic mice differs from that of murine P-selectin, resulting in distinct functions.

Cited by 72 publications

References 78 publications

Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo

Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo

Platelets lacking PIP5KIγ have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion

Silencing α1,3-Fucosyltransferases in Human Leukocytes Reveals a Role for FUT9 Enzyme during E-selectin-mediated Cell Adhesion

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