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Nitric oxide attenuates normal and sickle red blood cell adherence to pulmonary endothelium
Author(s) -
Space Sharon L.,
Lane Peter A.,
Pickett Cheryl K.,
Weil John V.
Publication year - 2000
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(200004)63:4<200::aid-ajh7>3.0.co;2-q
Subject(s) - endothelium , nitric oxide , medicine , sickle cell anemia , endothelial dysfunction , immunology , endothelial activation , endothelial stem cell , platelet , red blood cell , endocrinology , chemistry , disease , in vitro , biochemistry
Increased adherence of sickle red blood cells (RBC) to endothelium is implicated as an initiating event of vaso‐occlusion in sickle cell disease. Although much is known about the humoral influences of this interaction, there has been little investigation regarding endothelial contributions. Endothelial 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 inhibits RBC adherence to endothelium is unexplored. We tested this hypothesis with endothelial monolayers exposed to RBC from normal (Hb AA) and sickle cell (Hb SS) volunteers in a parallel plate flow chamber. To decrease NO production, endothelial monolayers were exposed to 100 μM nitro‐ L ‐arginine (NLA), an inhibitor of nitric oxide synthase, resulting in an 87% increase in normal RBC adherence ( P = 0.002). Because adherence of normal RBC to endothelium was low, the effect of DETA‐NO, an NO donor, was tested after activation of endothelium with TNF‐α increased adherence by 130% ( P < 0.001). Subsequent addition of 2 mM DETA‐NO produced a 75% decrease in adherence of normal RBC to endothelium ( P = 0.03). At baseline, sickle RBC were significantly 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 may be therapeutic in sickle cell disease.Am. J. Hematol. 63:200–204, 2000. © 2000 Wiley‐Liss, Inc.