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Demonstration of endothelial adhesion of sickle cells in vivo: a distinct
role for deformable sickle cell discocytes
ME Fabry, E Fine, V Rajanayagam, SM Factor, J Gore, M Sylla and RL Nagel
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
10461.
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.
Volume 79,
Issue 6,
pp. 1602-1611,
03/15/1992
Copyright © 1992 by The American Society of Hematology
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