Disease relevance of Sele

• To determine whether the PSGL-1-independent E-selectin ligand was physiologically important, we used a P- and E-selectin-dependent cutaneous contact hypersensitivity model [1].
• E-selectin-/- mice treated with anti-P-selectin mAb exhibited augmented lung fibrosis histologically, increased lung collagen deposition, and increased mortality compared to wild-type mice [2].
• Edema and hemorrhage were significantly reduced in P-selectin(-/-) mice compared with wild-type mice while they were not inhibited in E-selectin(-/-) mice [3].
• METHODS: Using our model of isolated ventilated lung from female mouse perfused with fresh blood from either isogeneic or allogeneic male mouse for 3 hours without noticeable ischemia, we have investigated the kinetics of the early events after endothelial cell triggering by E-selectin engagement [4].
• TBC-1269 reduced neutrophil recruitment in thioglycollate-induced peritonitis in wild-type and P-selectin-/- mice but not in E-selectin-/- mice [5].

High impact information on Sele

• Immigration of Th1 cells into inflamed skin can be blocked by antibodies against P- and E-selectin [6].
• Unlike CREB alpha/delta-deficient mice whose main defect is in long-term potentiation, the widespread abnormalities in ATF-2 mutant mice demonstrate its absolute requirement for skeletal and central nervous system development, and for maximal induction of select genes with CRE sites, such as E-selectin [7].
• E-SELECTIN is an inducible cell-adhesion molecule on endothelial cells, which mediates the binding of neutrophils and functions as a Ca(2+)-dependent lectin [8].
• ESL-1, with a structure essentially identical to that of a receptor, thus functions as a cell adhesion ligand of E-selectin [8].
• We have recently identified a 150K glycoprotein as the major ligand for E-selectin on myeloid cells, using a recombinant antibody-like form of mouse E-selectin as an affinity probe [8].

Chemical compound and disease context of Sele

• Therefore, bleomycin-induced lung fibrosis was examined in E-selectin-/- mice, P-selectin-/- mice, and E-selectin-/- mice treated with anti-P-selectin monoclonal antibody (mAb) in comparison of wild-type mice [2].
• Expression of all these adhesion molecules (ICAM-1, VCAM-1, E-selectin and alpha v integrin) was induced by growth of B16F1 melanoma cells in the peritoneal cavity of the mouse [9].
• CD44 enables slow leukocyte rolling on E-selectin expressed on inflamed endothelium in vivo and cooperates with P-selectin glycoprotein ligand-1 to recruit neutrophils into thioglycollate-induced peritonitis and staphylococcal enterotoxin A-injected skin pouch [10].
• Regulation of intestinal nuclear factor-kappaB activity and E-selectin expression during sepsis: a role for peroxynitrite [11].
• Intravenous infusion of Escherichia coli, which markedly elevates plasma lipopolysaccharide and TNF-alpha, increased mRNA for E-selectin but not P-selectin in baboons [12].

Biological context of Sele

• Furthermore, a subpopulation, which does not contain the most primitive hematopoietic progenitor cells, undergoes apoptosis following E-selectin-mediated adhesion [13].
• The preferential interaction of plasma cells with E-selectin, but not P-selectin, correlated with elevated alpha1,3-fucosyltransferase-VII messenger RNA levels, but selective down-regulation of core 2 beta1-6-N-glucosaminyltransferase levels, compared to B cells [14].
• Moreover, stable transfection of the human myeloid cell line K562 (which does not express PSGL-1) with alpha(1,3) fucosyltransferase VII alone was sufficient to recapitulate the E-selectin-mediated growth inhibition and apoptosis observed in hematopoietic progenitor cells [13].
• Although both P- and E-selectin are constitutively expressed on bone marrow endothelial cells, their role in the regulation of hematopoiesis has only recently been investigated [13].
• Wild-type mice underwent an intrascrotal reverse-passive Arthus model of immune complex-dependent inflammation and subsequently, leukocyte-endothelial cell interactions and P- and E-selectin expression were assessed in cremasteric postcapillary venules [15].

Anatomical context of Sele

• EL-246 recognized a 110-kD protein expressed on cells transfected with E-selectin cDNA and stained many postcapillary venules in inflamed human tonsil [16].
• L-selectin from human, but not from mouse neutrophils binds directly to E-selectin [17].
• Ritonavir also suppressed the expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin, which correlated with a functional decrease in leukocyte adhesion [18].
• We now demonstrate that adhesion to E-selectin inhibits the proliferation of human CD34+ cells isolated either from human umbilical cord blood, adult mobilized blood, or steady-state bone marrow [13].
• Our results thus underscore a major difference between mature myeloid cells and immature stem/progenitor cells in that E-selectin ligands cooperate with alpha4 integrin rather than P-selectin ligands [19].

Associations of Sele with chemical compounds

• We conclude that L-selectin on human neutrophils is a major glycoprotein ligand among very few glycoproteins that can be isolated by an E-selectin affinity matrix [17].
• Competitive assays to test homing of long-term repopulating stem cells revealed a drastic reduction (> 99%) of the homed stem cell activity when both alpha4 integrin and E-selectin functions were absent [19].
• This study reports the expression profile of VCAM-1 and E-selectin in various mouse tissues after lipopolysaccharide administration [20].
• L- and E-selectin binding to high endothelial venules and to the sulfated ligands was inhibitable by the carbohydrates, fucoidan and sialyl Lewis X, respectively [21].
• Mice deficient in E-selectin expression have been produced in order to examine the role of this selectin in leukocyte trafficking [22].

Physical interactions of Sele

• These studies confirmed that core-2 O-glycans attached to Thr-57 play a critical role in supporting L- and P-selectin-dependent rolling and revealed that additional binding sites support >75% of E-selectin-mediated rolling [23].
• The replacement of Trp 5 with Phe resulted in a change of peptide's secondary structure and increased binding with MAb and E-selectin, suggesting improved carbohydrate mimicry [24].
• Fluid-phase E-selectin bound to approximately 70% fewer sites on PSGL-1-/- than PSGL-1+/+ neutrophils [25].
• The E-selectin-ligand-1 (ESL-1) is a high affinity glycoprotein ligand which participates in the binding of mouse myeloid cells to E-selectin [26].
• We found that a large fraction of CD4+ T cells from inflamed colonic LP and from non-inflamed PC, mLN and S expressed high levels of P- and E-selectin-binding epitopes (P-Lhi) in transplanted scid mice, but not in congenic, immunocompetent control mice [27].

Regulatory relationships of Sele

• In agreement with the biochemical data, the anti-L-selectin mAb DREG56 inhibited rolling of human neutrophils on immobilized E-selectin-Ig but not on P-selectin-Ig [17].
• To study the in vivo function of PSGL-1, without the influence of other leukocyte proteins, the authors observed the interaction of PSGL-1-coated microspheres in mouse venules stimulated to express P- and/or E-selectin [28].
• Adhesion of the HL-60 myeloid cells to immobilized mouse E-selectin was completely inhibited by MAb RME-1 under static conditions and adhesion of rat polymorphonuclear leukocytes to recombinant mouse E-selectin was blocked under rotation condition [29].
• The P-selectin mRNA was transiently induced at early time points while up-regulation of the E-selectin mRNA was more prolonged [30].
• As time passed, CD62P-binding antigen-specific CD4 T cells with interferon gamma production potential accumulated preferentially at the site of antigen injection but only in recipients that expressed CD62E [31].

Other interactions of Sele

• We have quantitated the effect of deficiency for intercellular adhesion molecule (ICAM)-1, P-selectin, or E-selectin on atherosclerotic lesion formation at 20 wk of age in apolipoprotein (apo) E(-/-) (deficient) mice fed a normal chow diet [32].
• Rolling did not involve L-selectin, but was partially reduced in wild-type mice treated with antibodies to P- or E-selectin and in mice that were deficient in these two selectins [33].
• In vitro studies demonstrated that binding of recombinant mouse E-selectin chimera to PSGL-1(-/-) neutrophils was dramatically decreased in mice treated systemically but not locally with TNF-alpha [1].
• However, controversy exists regarding the importance of PSGL-1-dependent and -independent E-selectin rolling [1].
• Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation [20].

Analytical, diagnostic and therapeutic context of Sele

• Using rat complementary DNA probes for VCAM-1 and E-selectin, Northern blot analysis showed a marked increase in transcript levels for both adhesion molecules in lung, heart, and kidney [20].
• Remarkably, flow cytometric analysis revealed that the frequency of interferon-gamma-producing natural killer T (NKT) cells in the bronchoalveolar lavage was decreased in E-selectin-/- mice and E-selectin-/- mice treated with anti-P-selectin mAb compared with wild-type mice [2].
• Although immunoprecipitations showed that both murine and human L-selectin could recognize the sulfated ligands from high endothelial venules more efficiently than human E-selectin at the concentrations used, both L- and E-selectin chimeras could inhibit in vivo lymphocyte trafficking into peripheral lymph nodes equally well [21].
• In addition, the effect of TNF-alpha on endothelial-leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1 expression by means of Western blot analysis was compatible with the mRNA results [34].
• Allogeneic perfusion was characterized after 3 hours by an additional loose adhesion of lymphocytes mediated by the E-selectin and related to the allogeneic activation of endothelial cells [4].

References