P-selectin glycoprotein ligand-1–deficient mice have impaired leukocyte tethering to E-selectin under flow

Xia, Lijun; Sperandio, Markus; Yago, Tadayuki; McDaniel, J. Michael; Cummings, Richard D.; Pearson‐White, Sonia; Ley, Klaus; McEver, Rodger P.

doi:10.1172/jci14151

Cited by 78 publications

(61 citation statements)

References 62 publications

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“…We have found no correlation between the organ‐colonizing potential of BW‐O variants and their capacity to bind to P‐ or E‐selectin. Moreover, in rolling assays on immobilized E‐selectin or P‐selectin,37 none of these BW‐O variants exhibited detectable rolling on either P‐selectin or E‐selectin, whereas murine leukocytes rolled as previously documented (data not shown). Hence, the role of PSGL‐1 in hematogenous metastasis of the BW‐O variants is unlikely to be mediated through the aforementioned mechanisms.…”

Section: Discussionsupporting

confidence: 78%

The metastatic T‐cell hybridoma antigen/P‐selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas

Raes

Ghassabeh

Brys

et al. 2007

Intl Journal of Cancer

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Using variants of the murine BW5147 lymphoma cell-line, we have previously identified 3 monoclonal antibodies (MAbs) that discriminate between metastatic and nonmetastatic BW5147-derived T-cell hybridomas and lymphomas, as well as BW5147-unrelated T-lymphomas. These MAbs were reported to recognize an identical membrane-associated sialoglycoprotein, termed ''metastatic T-cell hybridoma antigen'' (MTH-Ag). Here, we document that the expression pattern of the MTH-Ag on metastatic and nonmetastatic BW5147 variants correlates with that of the P-selectin glycoprotein ligand 1 (PSGL-1), a sialomucin involved in leukocyte recruitment to sites of inflammation. Moreover, the MAbs against the MTH-Ag recognize PSGL-1 when it is transfected in MTH-Ag-negative BW5147 variants, suggesting that the MTH-Ag is PSGL-1. Overexpression of MTH-Ag/PSGL-1 in MTH-Ag-negative BW5147 variants did not affect their in vivo malignancy. Yet, down-regulation of MTH-Ag/PSGL-1 expression on metastatic, MTH-Ag-positive BW5147 variants, using an RNA interference (RNAi) approach, resulted, in a dose-dependent manner, in a significant reduction of liver and spleen colonization and a delay in mortality of the recipient mice upon intravenous inoculation.Collectively, these results demonstrate that, although MTH-Ag/ PSGL-1 overexpression alone may not be sufficient for successful dissemination and organ colonization, MTH-Ag/PSGL-1 plays a critical role in hematogenous metastasis of lymphoid cancer cells. ' 2007 Wiley-Liss, Inc.Key words: CD162; malignancy; liver metastasis P-selectin glycoprotein ligand-1 (PSGL-1, also called CD162) is a mucin-like sialylated surface membrane-associated glycoprotein that binds to not only P-selectin, but also E-and L-selectin

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Section: Discussionsupporting

confidence: 78%

The metastatic T‐cell hybridoma antigen/P‐selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas

Raes

Ghassabeh

Brys

et al. 2007

Intl Journal of Cancer

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“…In a flow chamber rolling assay, neutrophil adhesion to cells transfected with both E‐selectin to provide a rolling substrate and ICAM‐1 to provide an adhesion substrate was partially blocked by an antibody to PSGL‐1 (71). The physiological importance of this potential signaling through PSGL‐1 is not known, because the contribution of PSGL‐1 to E‐selectin‐dependent neutrophil capture and rolling may be limited, at least in some inflammatory conditions (72). Assays in which neutrophils are rolling on a cellular substrate cannot test whether signaling is direct or whether other cell surface molecules or soluble mediators may be involved.…”

Section: Neutrophil Activation Through Ligation Of Psgl‐1mentioning

confidence: 99%

“…Neutrophils rolling in inflamed venules engage P‐selectin (69) mainly through PSGL‐1 (72, 93), E‐selectin through PSGL‐1 and unknown ligands (72), L‐selectin through poorly defined endothelial ligands (69, 70), chemoattractants through their cognate G‐protein‐coupled receptors, and LFA‐1 and Mac‐1 by binding to unidentified endothelial ligands, possibly including ICAM‐1 (36, 41). This scenario provides ample opportunities for neutrophil activation.…”

Section: Integration Of Activating Signals By Rolling Neutrophilsmentioning

confidence: 99%

Integration of inflammatory signals by rolling neutrophils

Ley

2002

Immunological Reviews

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216

154

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In inflammation, neutrophils roll along the endothelial wall of postcapillary venules and sample inflammatory signals. Neutrophil activation is required to generate beta(2) integrin bonds with the endothelium that are strong enough to withstand the flow forces and thus achieve arrest from the rolling state. Unlike naïve T cells, neutrophils are not only activated by ligation of G-protein coupled receptors with chemokines and other chemoattractants but also receive signals from engagement of adhesion molecules including the selectins and beta(2) integrins. Rolling neutrophils integrate the sum total of inputs received while scanning the inflamed endothelium. In this process, the velocity of rolling neutrophils systematically decreases as a function of their contact time with the inflamed endothelium. If an activation threshold is reached, beta(2) integrins switch to the high-affinity conformation, redistribute on the cell surface, and trigger arrest and adhesion. Rolling cells that do not reach the activation threshold detach from the endothelium and are released back into the circulation. The role of chemokines, adhesion molecules, and other activating inputs involved in this response as well as signaling pathways are the subjects of ongoing investigations. This review provides a conceptual framework for neutrophil recruitment from the flowing blood.

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“…These inflammatory mediators induce the expression of E‐ and P‐selectin (Vestweber and Blanks, 1999). P‐selectin glycoprotein ligand‐1 (PSGL‐1) is the major ligand for P‐selectin (Moore et al ., 1992; Somers et al ., 2000); however, PSGL‐1 also interacts with E‐selectin (Xia et al ., 2002). Transient interactions between PSGL‐1 and these two selectins initiate rolling of leucocytes over the endothelium, the first step in recruitment of leucocytes to the site of infection.…”

Section: Introductionmentioning

confidence: 99%

Identification of an immunomodulating metalloprotease of Pseudomonas aeruginosa (IMPa)

Bardoel¹,

Hartsink²,

Vughs³

et al. 2012

Cellular Microbiology

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SummaryPhagocytosis by neutrophils is the essential step in fighting Pseudomonas infections. The first step in neutrophil recruitment to the site infection is the interaction of P-selectin (on endothelial cells) with P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils. Pseudomonas aeruginosa secretes various proteases that degrade proteins that are essential for host defence, such as elastase and alkaline protease. Here we identify PA0572 of P. aeruginosa as an inhibitor of PSGL-1 and named this secreted hypothetical protease immunomodulating metalloprotease of P. aeruginosa or IMPa. Proteolytic activity was confirmed by cleavage of recombinant and cell-surface expressed PSGL-1. Functional inhibition was demonstrated by impaired PSGL-1-mediated rolling of IMPa-treated neutrophils under flow conditions. Next to PSGL-1, IMPa targets CD43 and CD44 that are also involved in leucocyte homing. These data indicate that IMPa prevents neutrophil extravasation and thereby protects P. aeruginosa from neutrophil attack.

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P-selectin glycoprotein ligand-1–deficient mice have impaired leukocyte tethering to E-selectin under flow

Cited by 78 publications

References 62 publications

The metastatic T‐cell hybridoma antigen/P‐selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas

The metastatic T‐cell hybridoma antigen/P‐selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas

Integration of inflammatory signals by rolling neutrophils

Identification of an immunomodulating metalloprotease of Pseudomonas aeruginosa (IMPa)

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