Nitric oxide attenuates normal and sickle red blood cell adherence to pulmonary endothelium

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. (C) Wiley-Liss, Inc.