Abstract The human lymphocyte homing receptor, LAM-1, mediates the adhesion of lymphocytes to specialized high endothelial venules (HEV) peripheral lymph nodes. We now report that LAM-1 is also a major mediator leukocyte attachment activated endothelium. In novel assay, was shown mediate approximately 50% both and neutrophils TNF-activated umbilical vein cells at 4 degrees C. contribution only detectable when assays were carried out under rotating (nonstatic) conditions, suggesting involved...

Abstract There is increasing evidence that cytokines such as granulocyte-macrophage (GM)-CSF can profoundly affect the adhesion, aggregation, and mobility of neutrophils both in vitro vivo. However, mechanisms whereby these factors might alter adhesive properties are incompletely understood. A new family cellular adhesion molecules has recently been identified by cDNA cloning. The members this include human leukocyte molecule-1 (LAM-1), endothelial-leukocyte molecule, mouse homing receptor...

Selectins play a critical role in initiating leukocyte binding to vascular endothelium. In addition, vitro experiments have shown that neutrophils use L-selectin roll on adherent neutrophils, suggesting they express nonvascular ligand. Using L-selectin/IgM heavy chain (mu) chimeric protein as an immunocytological probe, we show here can bind monocytes, CD34+ hematopoietic progenitors, and HL-60 KG-1 myeloid cells. The interaction between leukocytes was protease sensitive calcium dependent,...

The leukocyte adhesion molecule-1 (LAM-1, TQ=1, Leu-8) in humans, like its murine homologue, MEL-14, is the principal receptor that mediates binding of leukocytes to high endothelial venules (HEV) peripheral lymph nodes. In this study, several regions protein which mediate function were identified by using a large panel mAb reactive with LAM-1. Individual reacted LAM-1+ cells characteristic intensities immunofluorescence staining, and each bound both lymphocytes neutrophils. Lymphocyte...

This study examines the role of L-selectin in monocyte adhesion to arterial endothelium, a key pathogenic event atherosclerosis. Using nonstatic (rotation) assay, we observed that binding bovine aortic endothelium at 4°C increased four nine times upon activation with tumor necrosis factor (TNF)-α. mAb-blocking experiments demonstrated mediates major part (64 ± 18%) attachment. Videomicroscopy performed under flow indicated monocytes abruptly halted on 8-h TNF-α–activated ∼80% attachment...

The role of L-selectin (LAM-1) as a regulator leukocyte adhesion to kidney microvascular glomerular endothelial cells was assessed in vitro by using L-selectin-directed mAb and an cDNA-transfected cell line. initial attachment neutrophils, monocytes, lymphocytes TNF-activated bovine significantly inhibited the anti-LAM1-3 mAb. Under static conditions, neutrophil 15 +/- 5%, whereas anti-LAM1-10 mAb, directed against functionally silent epitope L-selectin, without effect. binding CD18 47 6%....

The human lymphocyte homing receptor LAM-1, like its murine counterpart MEL-14, functions as a mammalian lectin, and mediates the binding of leukocytes to specialized high endothelial cells in lymphoid organs (HEV). LAM-1 is member new family cell adhesion molecules, termed selectins or LEC-CAMs, which also includes ELAM-1 PAD-GEM (GMP-140/CD62). To localize regions that are involved adhesion, we developed chimeric selectins, various domains were substituted into used these proteins define...

The leukocyte adhesion molecule-1 (LAM-1, TQ1, Leu-8), expressed by human lymphocytes, neutrophils, monocytes, and their precursors, is a member of the selectin family cellular adhesion/homing receptors which play important roles in leukocyte-endothelial cell interactions. These surface molecules contain an amino-terminal lectin-like domain followed epidermal growth factor-like variable number short consensus repeat sequences similar to those found C3/C4 binding proteins. In this report,...

Interactions between the leukocyte adhesion receptor L-selectin and P-selectin glycoprotein ligand-1 play an important role in regulating inflammatory response by mediating tethering rolling on adherent leukocytes. In this study, we have examined effect of post-translational modifications PSGL-1 including Tyr sulfation presentation sialylated fucosylated <i>O</i>-glycans for binding. The functional importance these was determined analyzing soluble binding CHO cells expressing various...

Selectins play a major role in the inflammatory reaction by initiating neutrophil attachment to activated vascular endothelium. Some heparin preparations can interact with L- and P-selectin; however, determinants required for inhibiting selectin-mediated cell adhesion have not yet been characterized. We now report that carboxyl-reduced sulfated (prepared chemical modifications of porcine intestinal mucosal leading replacement carboxylates <i>O</i>-sulfate groups) trestatin A sulfate...

P-selectin glycoprotein ligand-1 (PSGL-1) interactions with selectins regulate leukocyte migration in inflammatory lesions. In mice, selectin ligand activity regulating recruitment and lymphocyte homing into lymph nodes results from the sum of unequal contributions fucosyltransferase (FucT)-IV FucT-VII, FucT-VII playing a predominant role. Here we have examined role human FucT-IV -VII conferring L-selectin, P-selectin, E-selectin binding activities to PSGL-1. Lewis x (Le(x)) carbohydrate was...

Acute myeloid and lymphoblastic leukemia are poor prognosis hematologic malignancies, which disseminate from the bone marrow into blood. Blast interactions with selectins expressed by vascular endothelium promote development of drug resistance leukostasis. While role in initiating blast adhesion is established, our knowledge involved selectin ligands incomplete. Using various primary acute cells U937 monoblasts, we identified here functional myeloblasts lymphoblasts performing biochemical...

Abstract The malignant microenvironment plays a major role in the development of resistance to therapies and occurrence relapses acute myeloid leukemia (AML). We previously showed that interactions AML blasts with bone marrow macrophages (MΦ) shift their polarization towards protumoral (M2-like) phenotype, promoting drug resistance; we demonstrated inhibiting colony-stimulating factor-1 receptor (CSF1R) repolarizes MΦ an antitumoral (M1-like) phenotype other factors may be involved....

Abstract Background P-selectin glycoprotein ligand-1 (PSGL-1) plays a critical role in recruiting leukocytes inflammatory lesions by mediating leukocyte rolling on selectins. Core-2 O-glycosylation of N -terminal threonine and sulfation at least one tyrosine residue PSGL-1 are required for L- binding. Little information is available the intra- inter-species evolution primary structure. In addition, evolutionary conservation selectin binding site has not been previously examined detail....

Abstract The synthesis of α/β‐ L ‐fucosylated cysteamine, 3‐thiopropionic acid, and 3‐thioacetic acid derivatives as building blocks for the preparation S ‐neofucopeptides is shown. These compounds were used in new thiofucosides ( 8 α, 9 β, 10 22 24 26 α) that show affinity towards E‐ P‐selectins. They constitute a series hydrolytically stable low‐molecular‐weight mimetics natural SLe x tetrasaccharide. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)

P-selectin glycoprotein ligand-1 (PSGL-1) interacts with selectins to support leukocyte rolling along vascular wall. L- and bind N-terminal tyrosine sulfate residues core-2 O-glycans attached Thr-57, whereas sulfation is not required for E-selectin binding. PSGL-1 extracellular domain contains decameric repeats, which extend binding sites far above the plasma membrane. We hypothesized that decamers may play a role in regulating interactions selectins. Chinese hamster ovary cells expressing...

Abstract Platelet adhesion, the initial step of platelet activation, is mediated by interaction von Willebrand factor (VWF) with its receptor, GPIb–IX complex. The binding VWF to induced either increased shear stress or exogenous modulators, such as botrocetin. At a molecular level, this takes place between A1 domain and GPIbα chain We report here design functional characteristics template‐assembled synthetic protein (TASP), chimeric four‐helix‐bundle TASP scaffold mimicking surface domain....