During inflammation, E-selectin expressed on cytokine-activated endothelial cells mediates leukocyte rolling under flow. E-selectin undergoes endocytosis and may associate with lipid rafts. We asked whether distribution of E-selectin in membrane domains affects its functions. E-selectin was internalized in transfected CHO cells or cytokine-activated human umbilical vein endothelial cells (HUVEC...

Increased levels of soluble P-selectin (sP-selectin) have been shown in a number of different disorders, e.g. diabetes mellitus (DM) and cardiovascular disease (CVD). Several studies have attempted to demonstrate the association of the most intensively examined variant of P-selectin gene polymorphism (Thr715Pro) with sP-selectin levels in healthy subjects and in CVD, but contradictory data have...

E-selectin, an endothelial-specific adhesion molecule best known for its role in leukocyte adhesion, is not detected in quiescent endothelial cells, but is induced by inflammatory stimuli. However, E-selectin is also expressed in proliferating endothelial cells under noninflammatory conditions in vivo and in vitro, suggesting that E-selectin is also regulated by growth signals. To investigate E...

Hematogenous carcinoma metastasis is supported by aggregated platelets and leukocytes, forming tumor cell emboli. Early tumor cell-platelet interactions can be mediated by P-selectin binding to tumor cell surface ligands and this process is blocked by heparin. We previously showed that L-selectin deficiency also attenuates experimental metastasis. However, the mechanisms and timing of L-selecti...

The leukocyte adhesion molecule L-selectin mediates binding to lymph node high endothelial venules (HEV) and contributes to leukocyte rolling on endothelium at sites of inflammation. Previously, it was shown that truncation of the L-selectin cytoplasmic tail by 11 amino acids abolished binding to lymph node HEV and leukocyte rolling in vivo, but the molecular basis for that observation was not ...

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To assess the role of L-selectin and ICAM-1 in this pathogenetic process, the cutaneous reverse passive Arthus reaction was examined in mice lacking L-sel...

Thromb Haemost 2004; 92: 896–7 Asingle nucleotide polymorphism (SNP) in the P-selectin gene produces the Thr715Pro missense mutation. This affects the last consensus repeat which is adjacent to the transmembrane domain. Previous studies demonstrated that carriers of the C allele, which encodes for proline, have lower soluble P-selectin levels (1). Miller et al. (2) in this issue of Thrombosis a...

We examined the role of prostaglandin D2 (PGD2) in the formation of E-selectin following interleukin-1 (IL-1) stimulation in human umbilical vein endothelial cells (HUVEC) transfected with lipocaline-type PGD2 synthase (L-PGDS) genes. HUVEC were isolated from human umbilical vein and incubated with 20 U/mL IL-1 and various concentrations of authentic PGD2. The isolated HUVEC were also transfect...

BACKGROUND Endothelial E-selectin has been shown to play a pivotal role in mediating cell-cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for E-selectin and its role in mediating breast cancer cell transendothelial migration remain unknown. METHODOLOGY/PRINCIPAL FINDINGS By assessing migration of various breas...

BACKGROUND P-selectin mediates rolling of platelets and leukocytes on activated endothelial cells. After platelet activation, P-selectin is translocated from intracellular granules to the external membrane, whereas fibrinogen aggregates platelets by bridging glycoprotein (GP) IIb/IIIa between adjacent platelets. METHODS AND RESULTS In this study, we define a novel role for P-selectin in plate...