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Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes.

Abstract

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.

    , , , , ,

    Source

    Blood 79:6 1992 Mar 15 pg 1602-11

    MeSH

    Anemia, Sickle Cell
    Animals
    Cell Adhesion
    Deamino Arginine Vasopressin
    Edema
    Endothelium, Vascular
    Erythrocytes
    Female
    Humans
    Microcirculation
    Microscopy, Electron, Scanning
    Rats
    Rats, Inbred Strains
    Vascular Diseases

    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

    1547349

    Citation

    Fabry, M E., et al. "Demonstration of Endothelial Adhesion of Sickle Cells in Vivo: a Distinct Role for Deformable Sickle Cell Discocytes." Blood, vol. 79, no. 6, 1992, pp. 1602-11.
    Fabry ME, Fine E, Rajanayagam V, et al. Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes. Blood. 1992;79(6):1602-11.
    Fabry, M. E., Fine, E., Rajanayagam, V., Factor, S. M., Gore, J., Sylla, M., & Nagel, R. L. (1992). Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes. Blood, 79(6), pp. 1602-11.
    Fabry ME, et al. Demonstration of Endothelial Adhesion of Sickle Cells in Vivo: a Distinct Role for Deformable Sickle Cell Discocytes. Blood. 1992 Mar 15;79(6):1602-11. PubMed PMID: 1547349.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes. AU - Fabry,M E, AU - Fine,E, AU - Rajanayagam,V, AU - Factor,S M, AU - Gore,J, AU - Sylla,M, AU - Nagel,R L, PY - 1992/3/15/pubmed PY - 1992/3/15/medline PY - 1992/3/15/entrez SP - 1602 EP - 11 JF - Blood JO - Blood VL - 79 IS - 6 N2 - Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/1547349/Demonstration_of_endothelial_adhesion_of_sickle_cells_in_vivo:_a_distinct_role_for_deformable_sickle_cell_discocytes_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=1547349 DB - PRIME DP - Unbound Medicine ER -