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Thrombospondin from activated platelets promotes sickle erythrocyte
adherence to human microvascular endothelium under physiologic flow: a
potential role for platelet activation in sickle cell vaso-occlusion
HA Brittain, JR Eckman, RA Swerlick, RJ Howard and TM Wick
School of Chemical Engineering, Georgia Institute of Technology, Atlanta
30332-0100.
Adherence of erythrocytes to vascular endothelium likely contributes to the
pathophysiology of episodic vascular occlusion in patients with sickle cell
disease (SCD). In addition, coagulation activation has been reported in
sickle patients during complications such as pain episodes. To test the
hypothesis that platelet activation contributes to sickle erythrocyte
binding, we investigated whether factors released from activated sickle
platelets promote adherence of sickle erythrocytes to human microvascular
endothelial cells (MEC) under flow conditions. Activated sickle platelet
supernatant (ASPS) promoted high levels of sickle erythrocyte adherence to
MEC (55.4 +/- 3.9 erythrocytes/mm2) but only moderate adherence of normal
erythrocytes to MEC (14.1 +/- 0.7 erythrocytes/mm2). When MEC were
incubated with an antibody (OKM5) against CD36 (a thrombospondin [TSP]
receptor), platelet supernatant mediated sickle erythrocyte adherence was
inhibited 86%, suggesting that TSP participated in the adherence. To
further define the role of TSP in adherence, additional studies using
purified TSP were performed. At a concentration of 0.2 micrograms/mL TSP in
serum-free media (SFM), sickle erythrocyte adherence to MEC was 33.9 +/-
2.7 erythrocytes/mm2 and sixfold greater than either sickle erythrocyte
adherence in the absence of TSP or normal erythrocyte adherence in the
presence of TSP. Doubling the concentration of TSP to 0.4 micrograms/mL
proportionally increased adherence of sickle erythrocytes. Incubation of
MEC with OKM5 or anti-alpha v monoclonal antibodies inhibited TSP-mediated
sickle erythrocyte adherence more than 95%. These data suggest that
activated platelet release factors, including alpha-granule TSP, which
promote receptor-mediated sickle erythrocyte adherence to microvascular
endothelium. Such factors released during in vivo platelet activation could
contribute to vaso-occlusive complications by promoting erythrocyte
adherence and microvascular occlusion.
Volume 81,
Issue 8,
pp. 2137-2143,
04/15/1993
Copyright © 1993 by The American Society of Hematology
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