Increased adherence of sickle red blood cells (RBC) to endothelium is impli
cated as an initiating event of vaso-occlusion In sickle cell disease. Alth
ough much is known about the humoral influences of this interaction, there
has been little investigation regarding endothelial contributions. Endothel
ial derived nitric oxide (NO) inhibits adhesion of platelets and leukocytes
to endothelium and decreases expression of VCAM-1, an endothelial adhesion
site Implicated in sickle RBC/endothelial adherence. However, whether NO i
nhibits RBC adherence to endothelium is unexplored. We tested this hypothes
is with endothelial monolayers exposed to RBC from normal (Hb AA) and sickl
e cell (Hb SS) volunteers in a parallel plate flow chamber. To decrease NO
production, endothelial monolayers were exposed to 100 mu M nitro-L-arginin
e (NLA), an inhibitor of nitric oxide synthase, resulting in an 87% increas
e in normal RBC adherence (P = 0.002). Because adherence of normal RBC to e
ndothelium was low, the effect of DETA-NO, an NO donor, was tested after ac
tivation of endothelium with TNF-alpha increased adherence by 130% (P < 0.0
01). Subsequent addition of 2 mM DETA-NO produced a 75% decrease in adheren
ce of normal RBC to endothelium (P = 0.03). At baseline, sickle RBC were si
gnificantly more adherent than normal RBC (P < 0.001) and DETA-NO decreased
sickle RBC adherence by 54% (P = 0.04). Thus, NO inhibits both normal and
sickle RBC adherence to endothelium. Strategies that enhance NO activity ma
y be therapeutic in sickle cell disease. Am. J. Hematol. 63:200-204, 2000.
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