Species-Specific and Conserved Epitopes on Mouse and Human E-Selectin Important for Leukocyte Adhesion

Hammel, M; Weitz‐Schmidt, Gabriele; Krause, A.; Moll, Thomas; Vestweber, Dietmar; Zerwes, Hans‐Günter; Hallmann, Rupert

doi:10.1006/excr.2001.5317

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…Mouse monoclonal antibodies used for the detection of LBPA (clone 6C4; 1:50) 21 were kindly provided by Jean Gruenberg (University of Geneva, Geneva, Switzerland) and mouse monoclonal antibodies used for the visualization of internalized CD63 (clone 1B5; 1:300; 1:100 for surface staining) 32 were a kind gift from Mark Marsh (University College London). Rat UZ4 monoclonal antibodies used for the detection of surface E-selectin (1:2) were kindly provided by Rupert Hallmann (University Hospital Münster, Germany) 33 . Secondary anti-mouse antibodies coupled to Alexa Fluor 488 (1:400) or Alexa Fluor 568 (1:400) were obtained from Molecular Probes (Eugene, OR, USA); horseradish peroxidase-conjugated anti-mouse or antigoat antibodies (1:2,000) were obtained from Dako (Hamburg, Germany); TRITCconjugated secondary anti-sheep antibodies (1:200) and anti-mouse antibodies coupled to Cy5 (1:100) were obtained from Jackson ImmunoResearch (Newmarket, Suffolk, UK).…”

Section: Discussionmentioning

confidence: 99%

Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63

et al. 2014

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To enable leukocyte adhesion to activated endothelium, the leukocyte receptor P-selectin is released from Weibel-Palade bodies (WPB) to the endothelial cell surface where it is stabilized by CD63. Here we report that loss of annexin A8 (anxA8) in human umbilical vein endothelial cells (HUVEC) strongly decreases cell surface presentation of CD63 and P-selectin, with a concomitant reduction in leukocyte rolling and adhesion. We confirm the compromised leukocyte adhesiveness in inflammatory-activated endothelial venules of anxA8-deficient mice. We find that WPB of anxA8-deficient HUVEC contain less CD63, and that this is caused by improper transport of CD63 from late multivesicular endosomes to WPB, with CD63 being retained in intraluminal vesicles. Consequently, reduced CD63 cell surface levels are seen following WPB exocytosis, resulting in enhanced P-selectin re-internalization. Our data support a model in which anxA8 affects leukocyte recruitment to activated endothelial cells by supplying WPB with sufficient amounts of the P-selectin regulator CD63.

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Section: Discussionmentioning

confidence: 99%

Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63

et al. 2014

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“…Antibodies against mouse P-selectin (clone RB40/34; Bosse and Vestweber, 1994), mouse E-selectin (clone UZ4; Hammel et al, 2001), mouse VEcadherin (polyclonal serum C5 and clone 11D4), and ESAM (VE19) have been described previously (Gotsch et al, 1997;Nasdala et al, 2002). pAbs against JAM-A ( Khandoga et al, 2009) and mAb against mouse VCAM-1 (Hahne et al, 1993) are as previously described.…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo

Schnoor¹,

Lai²,

Zarbock³

et al. 2011

J Cell Biol

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The maintenance of vascular barrier integrity is crucial during many pathophysiological processes and requires coordinated molecular events including signaling and cytoskeletal remodeling. Cortactin is an actin‐binding protein that regulates actin dynamics and related signaling events. To analyze the role of cortactin in vascular barrier functions, we generated cortactin‐deficient mice. Classical Miles assays revealed that vascular permeability is increased in these mice. Despite this leakiness, leukocyte extravasation in the TNF‐α‐stimulated cremaster was inhibited. Mechanistically, the permeability defect in the absence of cortactin was caused by reduced levels of active Rap1 in endothelial cells and could be rescued by activating Rap1 via the GTPase exchange factor EPAC. The defect in leukocyte extravasation was due to impaired interactions between leukocytes and endothelial cells, as documented by an increased rolling velocity and decreased numbers of adhering leukocytes in postcapillary venules. Impaired rolling interactions were linked to contributions of β2‐integrin‐ligands to this process and firm adhesion was compromised by the loss of ICAM‐1‐containing leukocyte docking structures. These results are the first physiological evidence that cortactin is crucial for orchestrating molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

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“…4B). To validate the central role of E-selectin, anti-E-selectin mAb 16A (UZ4) was infused before injection of PC-3 FT cells (24). As a result, PC-3 FT cell binding to inflamed venules was blocked ( Fig.…”

Section: Ft3 Ft6 and Ft7 Induce E-selectin-mediated Adhesion Of Metmentioning

confidence: 99%

Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking

Barthel

Wiese

Cho

et al. 2009

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

112

117

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How cancer cells bind to vascular surfaces and extravasate into target organs is an underappreciated, yet essential step in metastasis. We postulate that the metastatic process involves discrete adhesive interactions between circulating cancer cells and microvascular endothelial cells. Sialyl Lewis X (sLe X ) on prostate cancer (PCa) cells is thought to promote metastasis by mediating PCa cell binding to microvascular endothelial (E)-selectin. Yet, regulation of sLe X and related E-selectin ligand expression in PCa cells is a poorly understood factor in PCa metastasis. Here, we describe a glycobiological mechanism regulating E-selectin-mediated adhesion and metastatic potential of PCa cells. We demonstrate that ␣1,3 fucosyltransferases (FT) 3, 6, and 7 are markedly elevated in bone-and liver-metastatic PCa and dictate synthesis of sLe X and E-selectin ligands on metastatic PCa cells. (1). Delineating mediators of PCa metastasis to target organs may lead to identification of prognostic biomarkers and anti-metastatic therapeutics. Recently, our lab has advanced a scenario to account for organ metastasis involving PCa cell adhesion to surface receptors expressed on microvascular endothelial cells of the target organ (2-4). Bone-metastatic PCa cells are known to attach more avidly to bone marrow endothelial cells (BMEC) compared with endothelial linings of nontarget organs (5, 6). For example, human bone-metastatic PCa MDA PCa 2b (MDA) cells roll and adhere on BMEC by binding endothelial (E)-selectin, raising the possibility that PCa metastasis could be conferred through E-selectin Ϫ E-selectin ligand adhesive interactions (2-4). In fact, BM microvessels express E-selectin constitutively, while E-selectin is inducible on endothelial linings of inflamed tissues and of bronchial mucosa, a common PCa target tissue (7-9). Mechanistically, an identical traffic control axis involving selectins is well-known in the extravasation of hematopoietic progenitor cells (HPC) into BM (10, 11). HPC rolling on E-and platelet (P)-selectin is regulated by sLe X -bearing glycoforms of CD44 (HCELL), PSGL-1 and glycolipids (10,12,13). Synthesis of sLe X in HPC is catalyzed in the Golgi compartment by members of the glycosyltransferase gene family (14). The final step involves the transfer of fucose to N-acetylglucosamine at the terminal ␣2,3 sialo-lactosamine unit by ␣1,3 fucosyltransferases (FT) 3, 4, 5, 6, and/or 7, depending on cell type (13, 15). That metastatic PCa cells traverse the vasculature through 'hematopoietic mimicry' is consistent with several observations, including the association of sLe X with PCa grade and progression (2, 16, 17), cancer cell E-selectin ligand activity is a direct correlate with metastatic potential (18,19) and cancer cells can trigger E-selectin expression on liver sinusoidal microvasculature to steer circulating cancer cells to the liver (20,21). Thus, mapping glyco-metabolic pathways regulating E-selectin ligand synthesis may be vital for understanding PCa metastasis.In this report, we identify E-s...

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Species-Specific and Conserved Epitopes on Mouse and Human E-Selectin Important for Leukocyte Adhesion

Cited by 19 publications

References 36 publications

Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63

Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo

Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking

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