Multiple Selectin Blockade with a Small Molecule Inhibitor Downregulates Liver Chemokine Expression and Neutrophil Infiltration after Hemorrhagic Shock

Ramos-Kelly, J. Ricardo; Toledo‐Pereyra, Luis H.; Jordan, James O.; Rivera-Chavez, Fernando A.; Rohs, Thomas; Holevar, M.; Dixon, Richard A. F.; Yun, Edward C.; Ward, Peter A.

doi:10.1097/00005373-200007000-00015

Cited by 23 publications

(15 citation statements)

References 32 publications

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“…Since AAG treatment significantly decreased the levels of AST and ALT, it suggests that this agent prevents/decreases the subsequent liver damage following trauma-hemorrhage and resuscitation. Based on previous studies [26], we postulate that the decreased leukocyte infiltration could be responsible for this protection. However, other potential protective mechanism such as the prevention of TNF-␣-induced apoptosis [27] or the modulation of platelet aggregation [3] could also play an important role in the observed beneficial effects.…”

Section: Discussionmentioning

confidence: 73%

Alpha1-acid-glycoprotein protects against trauma-hemorrhagic shock

Kuebler

Tóth

Yokoyama

et al. 2004

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 73%

Alpha1-acid-glycoprotein protects against trauma-hemorrhagic shock

Kuebler

Tóth

Yokoyama

et al. 2004

Journal of Surgical Research

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“…Here, we report that E-selectin-mediated coclustering of L-selectin and PSGL-1 was dependent on lectin domain recognition of sLe x . Remarkably, pretreatment of E-selectin with the di-sLe x mimetic TBC1269, a small molecule currently being studied as an anti-inflammatory therapeutic, had a greater affect on the transition to arrest than did capture and rolling of neutrophils in the PPFC (26,42,43). Inhibition with TBC1269 increased the fraction of rolling neutrophils by ϳ25%, but decreased arrest by ϳ50%.…”

Section: Recognition Of Sle X On L-selectin and Psgl-1 By E-selectin mentioning

confidence: 99%

Shear-Dependent Capping of L-Selectin and P-Selectin Glycoprotein Ligand 1 by E-Selectin Signals Activation of High-Avidity β2-Integrin on Neutrophils

Green

Pearson

Camphausen³

et al. 2004

The Journal of Immunology

116

129

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Two adhesive events critical to efficient recruitment of neutrophils at vascular sites of inflammation are up-regulation of endothelial selectins that bind sialyl Lewisx ligands and activation of β2-integrins that support neutrophil arrest by binding ICAM-1. We have previously reported that neutrophils rolling on E-selectin are sufficient for signaling cell arrest through β2-integrin binding of ICAM-1 in a process dependent upon ligation of L-selectin and P-selectin glycoprotein ligand 1 (PSGL-1). Unresolved are the spatial and temporal events that occur as E-selectin binds to human neutrophils and dynamically signals the transition from neutrophil rolling to arrest. Here we show that binding of E-selectin to sialyl Lewisx on L-selectin and PSGL-1 drives their colocalization into membrane caps at the trailing edge of neutrophils rolling on HUVECs and on an L-cell monolayer coexpressing E-selectin and ICAM-1. Likewise, binding of recombinant E-selectin to PMNs in suspension also elicited coclustering of L-selectin and PSGL-1 that was signaled via mitogen-activated protein kinase. Binding of recombinant E-selectin signaled activation of β2-integrin to high-avidity clusters and elicited efficient neutrophil capture of β2-integrin ligands in shear flow. Inhibition of p38 and p42/44 mitogen-activated protein kinase blocked the cocapping of L-selectin and PSGL-1 and the subsequent clustering of high-affinity β2-integrin. Taken together, the data suggest that E-selectin is unique among selectins in its capacity for clustering sialylated ligands and transducing signals leading to neutrophil arrest in shear flow.

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“…Our group has performed extensive work to determine the function, biochemistry, and molecular biology of the ischemic injury [52][53][54][55][56][57][58][59][60][61]. We have found that the Akt pathway plays an essential role in the phosphoregulation of acute inflammatory processes secondary to I/R injury.…”

Section: Phosphoregulation Of Inflammation Secondary To I/r: Our Currmentioning

confidence: 99%