Tags

Type your tag names separated by a space and hit enter

Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium.

Abstract

Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens are both carried by two glycoprotein (gp) isoforms of the immunoglobulin superfamily representing receptors for laminin alpha5 chain. They are expressed in red blood cells, in endothelial cells of vascular capillaries and in epithelial cells of several tissues. Lu/BCAM gps are overexpressed in sickle red blood cells (SS RBCs). Stimulation of SS RBCs by epinephrine activates the PKA depending signaling pathway and induces reinforced Lu/BCAM-mediated adhesion to laminin10/11. We have analyzed the phosphorylation state of Lu/BCAM long isoform cytoplasmic tail and showed that it is phosphorylated by CKII, GSK3b and PKA. Phosphorylation of this isoform in transfected K562 cells is stimulated by effectors of the PKA pathway and induces cell adhesion to laminin10/11. Lu/BCAM gps are highly expressed in endothelial cells and exhibit potential integrin binding motifs. We showed that they interact with integrin alpha4beta1, the unique integrin expressed on the surface of young reticulocytes. Adhesion assays under flow conditions showed that SS RBCs adhere to primary human endothelial cells (HUVEC) after selective activation of intergin alpha4beta1 and that this adhesion is mediated by endothelial Lu/BCAM gps. Our studies show that Lu/BCAM gps expressed either on erythroid or on endothelial cells are involved in SS RBC-endothelium interactions and could play a role in the abnormal adhesion of SS RBCs to vascular endothelium contributing to the vaso-occlusive crises reported for sickle cell disease patients.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Inserm U665, 75015 Paris, France. wassim.el-nemer@inserm.fr

    , , , , , , , ,

    Source

    MeSH

    Anemia, Sickle Cell
    Cell Adhesion
    Cell Adhesion Molecules
    Endothelium, Vascular
    Epinephrine
    Erythrocytes
    Humans
    Integrin alpha4beta1
    Lutheran Blood-Group System
    Neoplasm Proteins

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    18514010

    Citation

    El Nemer, W, et al. "Role of Lu/BCAM in Abnormal Adhesion of Sickle Red Blood Cells to Vascular Endothelium." Transfusion Clinique Et Biologique : Journal De La Societe Francaise De Transfusion Sanguine, vol. 15, no. 1-2, 2008, pp. 29-33.
    El Nemer W, Gauthier E, Wautier MP, et al. Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium. Transfus Clin Biol. 2008;15(1-2):29-33.
    El Nemer, W., Gauthier, E., Wautier, M. P., Rahuel, C., Gane, P., Galactéros, F., ... Le Van Kim, C. (2008). Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium. Transfusion Clinique Et Biologique : Journal De La Societe Francaise De Transfusion Sanguine, 15(1-2), pp. 29-33. doi:10.1016/j.tracli.2008.05.002.
    El Nemer W, et al. Role of Lu/BCAM in Abnormal Adhesion of Sickle Red Blood Cells to Vascular Endothelium. Transfus Clin Biol. 2008;15(1-2):29-33. PubMed PMID: 18514010.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium. AU - El Nemer,W, AU - Gauthier,E, AU - Wautier,M-P, AU - Rahuel,C, AU - Gane,P, AU - Galactéros,F, AU - Wautier,J-L, AU - Cartron,J-P, AU - Colin,Y, AU - Le Van Kim,C, Y1 - 2008/06/02/ PY - 2008/05/06/received PY - 2008/05/06/accepted PY - 2008/6/3/pubmed PY - 2008/9/16/medline PY - 2008/6/3/entrez SP - 29 EP - 33 JF - Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine JO - Transfus Clin Biol VL - 15 IS - 1-2 N2 - Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens are both carried by two glycoprotein (gp) isoforms of the immunoglobulin superfamily representing receptors for laminin alpha5 chain. They are expressed in red blood cells, in endothelial cells of vascular capillaries and in epithelial cells of several tissues. Lu/BCAM gps are overexpressed in sickle red blood cells (SS RBCs). Stimulation of SS RBCs by epinephrine activates the PKA depending signaling pathway and induces reinforced Lu/BCAM-mediated adhesion to laminin10/11. We have analyzed the phosphorylation state of Lu/BCAM long isoform cytoplasmic tail and showed that it is phosphorylated by CKII, GSK3b and PKA. Phosphorylation of this isoform in transfected K562 cells is stimulated by effectors of the PKA pathway and induces cell adhesion to laminin10/11. Lu/BCAM gps are highly expressed in endothelial cells and exhibit potential integrin binding motifs. We showed that they interact with integrin alpha4beta1, the unique integrin expressed on the surface of young reticulocytes. Adhesion assays under flow conditions showed that SS RBCs adhere to primary human endothelial cells (HUVEC) after selective activation of intergin alpha4beta1 and that this adhesion is mediated by endothelial Lu/BCAM gps. Our studies show that Lu/BCAM gps expressed either on erythroid or on endothelial cells are involved in SS RBC-endothelium interactions and could play a role in the abnormal adhesion of SS RBCs to vascular endothelium contributing to the vaso-occlusive crises reported for sickle cell disease patients. SN - 1246-7820 UR - https://www.unboundmedicine.com/medline/citation/18514010/Role_of_Lu/BCAM_in_abnormal_adhesion_of_sickle_red_blood_cells_to_vascular_endothelium_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1246-7820(08)00098-0 DB - PRIME DP - Unbound Medicine ER -