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Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes.

Abstract

The abnormal adherence of sickle red blood cells (SS RBC) to endothelial cells has been thought to contribute to vascular occlusion, a major cause of morbidity in sickle cell disease (SCD). We determined whether the interaction of SS RBC with cultured endothelial cells induced cellular oxidant stress that would culminate in expression of cell adhesion molecules (CAMs) involved in the adhesion and diapedesis of monocytes and the adherence of SS reticulocytes. We showed that the interaction of SS RBC at 2% concentration in the presence of multimers of von Willebrand factor (vWf), derived from endothelial cell-derived conditioned medium (E-CM) with cultured human umbilical vein endothelial cells (HUVEC), resulted in a fivefold increased formation of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-kB, both indicators of cellular oxidant stress. Normal RBC show none of these phenomena. The oxidant stress-induced signaling resulted in an increased surface expression of a subset of CAMs, ICAM-1, E-selectin, and VCAM-1 in HUVEC. The addition of oxygen radical scavenger enzymes (catalase, superoxide dismutase) and antioxidant (probucol) inhibited these events. Additionally, preincubation of HUVEC with a synthetic peptide Arg-Gly-Asp (RGD) that prevents vWf-mediated adhesion of SS RBC reduced the surface expression of VCAM-1 and NF-kB activation. Furthermore, SS RBC-induced oxidant stress resulted in a twofold increase in the transendothelial migration of both monocyte-like HL-60 cells and human peripheral blood monocytes, and approximately a sixfold increase in platelet-endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation, each of which was blocked by protein kinase C inhibitor and antioxidants. These results suggest that the adherence/contact of SS RBC to endothelial cells in large vessel can generate enhanced oxidant stress leading to increased adhesion and diapedesis of monocytes, as well as heightened adherence of SS reticulocytes, indicating that injury/activation of endothelium can contribute to vaso-occlusion in SCD.

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  • Authors+Show Affiliations

    ,

    Departments of Biochemistry and Molecular Biology, and Medicine, University of Southern California, School of Medicine, Los Angeles, CA, USA.

    , , ,

    Source

    Blood 92:10 1998 Nov 15 pg 3924-35

    MeSH

    Anemia, Sickle Cell
    Arterial Occlusive Diseases
    Cell Adhesion
    Cell Adhesion Molecules
    Cells, Cultured
    Chemotaxis, Leukocyte
    Culture Media, Conditioned
    Endothelium, Vascular
    Erythrocytes, Abnormal
    Humans
    Monocytes
    NF-kappa B
    Oxidative Stress
    Phosphorylation
    Platelet Endothelial Cell Adhesion Molecule-1
    Protein Processing, Post-Translational
    Reticulocytes
    Thiobarbituric Acid Reactive Substances
    Transcription, Genetic
    Umbilical Veins
    von Willebrand Factor

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    9808586

    Citation

    Sultana, C, et al. "Interaction of Sickle Erythrocytes With Endothelial Cells in the Presence of Endothelial Cell Conditioned Medium Induces Oxidant Stress Leading to Transendothelial Migration of Monocytes." Blood, vol. 92, no. 10, 1998, pp. 3924-35.
    Sultana C, Shen Y, Rattan V, et al. Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes. Blood. 1998;92(10):3924-35.
    Sultana, C., Shen, Y., Rattan, V., Johnson, C., & Kalra, V. K. (1998). Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes. Blood, 92(10), pp. 3924-35.
    Sultana C, et al. Interaction of Sickle Erythrocytes With Endothelial Cells in the Presence of Endothelial Cell Conditioned Medium Induces Oxidant Stress Leading to Transendothelial Migration of Monocytes. Blood. 1998 Nov 15;92(10):3924-35. PubMed PMID: 9808586.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes. AU - Sultana,C, AU - Shen,Y, AU - Rattan,V, AU - Johnson,C, AU - Kalra,V K, PY - 1998/11/10/pubmed PY - 1998/11/10/medline PY - 1998/11/10/entrez SP - 3924 EP - 35 JF - Blood JO - Blood VL - 92 IS - 10 N2 - The abnormal adherence of sickle red blood cells (SS RBC) to endothelial cells has been thought to contribute to vascular occlusion, a major cause of morbidity in sickle cell disease (SCD). We determined whether the interaction of SS RBC with cultured endothelial cells induced cellular oxidant stress that would culminate in expression of cell adhesion molecules (CAMs) involved in the adhesion and diapedesis of monocytes and the adherence of SS reticulocytes. We showed that the interaction of SS RBC at 2% concentration in the presence of multimers of von Willebrand factor (vWf), derived from endothelial cell-derived conditioned medium (E-CM) with cultured human umbilical vein endothelial cells (HUVEC), resulted in a fivefold increased formation of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-kB, both indicators of cellular oxidant stress. Normal RBC show none of these phenomena. The oxidant stress-induced signaling resulted in an increased surface expression of a subset of CAMs, ICAM-1, E-selectin, and VCAM-1 in HUVEC. The addition of oxygen radical scavenger enzymes (catalase, superoxide dismutase) and antioxidant (probucol) inhibited these events. Additionally, preincubation of HUVEC with a synthetic peptide Arg-Gly-Asp (RGD) that prevents vWf-mediated adhesion of SS RBC reduced the surface expression of VCAM-1 and NF-kB activation. Furthermore, SS RBC-induced oxidant stress resulted in a twofold increase in the transendothelial migration of both monocyte-like HL-60 cells and human peripheral blood monocytes, and approximately a sixfold increase in platelet-endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation, each of which was blocked by protein kinase C inhibitor and antioxidants. These results suggest that the adherence/contact of SS RBC to endothelial cells in large vessel can generate enhanced oxidant stress leading to increased adhesion and diapedesis of monocytes, as well as heightened adherence of SS reticulocytes, indicating that injury/activation of endothelium can contribute to vaso-occlusion in SCD. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9808586/Interaction_of_sickle_erythrocytes_with_endothelial_cells_in_the_presence_of_endothelial_cell_conditioned_medium_induces_oxidant_stress_leading_to_transendothelial_migration_of_monocytes_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9808586 DB - PRIME DP - Unbound Medicine ER -