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Rheological studies of erythrocyte-endothelial cell interactions in sickle cell disease.

Abstract

The abnormal adherence of sickle erythrocytes to endothelial cells (EC) has been hypothesized to play a role in the initiation of vaso-occlusion in sickle cell anemia. We studied erythrocyte/endothelial cell interactions under controlled flow conditions for normal (AA), homozygous sickle cell (SS), sickle cell trait (AS), mechanically injured normal, and "high reticulocyte control" red blood cells (RBC). Human umbilical vein endothelial cells grown to confluence on glass slides formed the base of a parallel plate flow chamber into which RBC suspensions were perfused at a constant flow rate, producing a wall shear stress of 1 dyne/cm2. Adhesion was monitored using video microscopy, and the number of adherent RBC was determined at ten-minute intervals during a wash out period. Results indicate that SS RBC were more adherent than AA RBC. Mechanically injured (sheared) RBC were also more adherent than control normal cells, but less adherent than SS RBC. AS RBC did not differ significantly in their adhesive properties from normal RBC. Less dense (younger) RBC were more adherent to EC than dense (older) cells for normal, SS and "high reticulocyte control" RBC. These findings suggest that the increased adhesion of sickle RBC is at least partially related to the increased numbers of young RBC present. Increased adherence of young cells to the EC lining vessel walls could contribute to microvascular occlusion by lengthening vascular transit times of other sickle cells. Microvascular occlusion is a major clinical problem in sickle cell anemia. This obstruction to blood flow could be due to decreased deformability of the cell and its inability to pass through small vessels. If this were the case it would be reasonable to expect that the most severely deformed sickle cells, the irreversibly sickled RBC (ISC), would play an important role in the initiation of vaso-occlusion. However, the number of circulating ISC is not well correlated with the frequency of painful crises and other microvascular occlusive phenomena. Recent evidence suggests that microvascular occlusion may be associated with increased adhesion of sickle cells to vascular endothelial cells. A strong correlation between erythrocyte adherence and clinical vaso-occlusive severity has been reported by Hebbel et al. Hoover et al. and Hebbel et al. demonstrated increased adhesion in static tests.(

ABSTRACT

TRUNCATED AT 400 WORDS)

Links

  • clinical trials
  • Authors

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    Source

    MeSH

    Anemia, Sickle Cell
    Biomechanical Phenomena
    Cell Adhesion
    Cells, Cultured
    Endothelium
    Erythrocytes
    Humans
    In Vitro Techniques
    Rheology

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    3615482

    Citation

    Barabino, G A., et al. "Rheological Studies of Erythrocyte-endothelial Cell Interactions in Sickle Cell Disease." Progress in Clinical and Biological Research, vol. 240, 1987, pp. 113-27.
    Barabino GA, McIntire LV, Eskin SG, et al. Rheological studies of erythrocyte-endothelial cell interactions in sickle cell disease. Prog Clin Biol Res. 1987;240:113-27.
    Barabino, G. A., McIntire, L. V., Eskin, S. G., Sears, D. A., & Udden, M. (1987). Rheological studies of erythrocyte-endothelial cell interactions in sickle cell disease. Progress in Clinical and Biological Research, 240, pp. 113-27.
    Barabino GA, et al. Rheological Studies of Erythrocyte-endothelial Cell Interactions in Sickle Cell Disease. Prog Clin Biol Res. 1987;240:113-27. PubMed PMID: 3615482.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Rheological studies of erythrocyte-endothelial cell interactions in sickle cell disease. AU - Barabino,G A, AU - McIntire,L V, AU - Eskin,S G, AU - Sears,D A, AU - Udden,M, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 113 EP - 27 JF - Progress in clinical and biological research JO - Prog. Clin. Biol. Res. VL - 240 N2 - The abnormal adherence of sickle erythrocytes to endothelial cells (EC) has been hypothesized to play a role in the initiation of vaso-occlusion in sickle cell anemia. We studied erythrocyte/endothelial cell interactions under controlled flow conditions for normal (AA), homozygous sickle cell (SS), sickle cell trait (AS), mechanically injured normal, and "high reticulocyte control" red blood cells (RBC). Human umbilical vein endothelial cells grown to confluence on glass slides formed the base of a parallel plate flow chamber into which RBC suspensions were perfused at a constant flow rate, producing a wall shear stress of 1 dyne/cm2. Adhesion was monitored using video microscopy, and the number of adherent RBC was determined at ten-minute intervals during a wash out period. Results indicate that SS RBC were more adherent than AA RBC. Mechanically injured (sheared) RBC were also more adherent than control normal cells, but less adherent than SS RBC. AS RBC did not differ significantly in their adhesive properties from normal RBC. Less dense (younger) RBC were more adherent to EC than dense (older) cells for normal, SS and "high reticulocyte control" RBC. These findings suggest that the increased adhesion of sickle RBC is at least partially related to the increased numbers of young RBC present. Increased adherence of young cells to the EC lining vessel walls could contribute to microvascular occlusion by lengthening vascular transit times of other sickle cells. Microvascular occlusion is a major clinical problem in sickle cell anemia. This obstruction to blood flow could be due to decreased deformability of the cell and its inability to pass through small vessels. If this were the case it would be reasonable to expect that the most severely deformed sickle cells, the irreversibly sickled RBC (ISC), would play an important role in the initiation of vaso-occlusion. However, the number of circulating ISC is not well correlated with the frequency of painful crises and other microvascular occlusive phenomena. Recent evidence suggests that microvascular occlusion may be associated with increased adhesion of sickle cells to vascular endothelial cells. A strong correlation between erythrocyte adherence and clinical vaso-occlusive severity has been reported by Hebbel et al. Hoover et al. and Hebbel et al. demonstrated increased adhesion in static tests.(ABSTRACT TRUNCATED AT 400 WORDS) SN - 0361-7742 UR - https://www.unboundmedicine.com/medline/citation/3615482/Rheological_studies_of_erythrocyte_endothelial_cell_interactions_in_sickle_cell_disease_ L2 - https://ClinicalTrials.gov/search/term=3615482 [PUBMED-IDS] DB - PRIME DP - Unbound Medicine ER -