Red blood cells express a functional endothelial nitric oxide synthase.
The synthesis of nitric oxide (NO) in the circulation has been attributed exclusively to the vascular endothelium. Red blood cells (RBCs) have been demonstrated to carry a nonfunctional NO synthase (NOS) and, due to their huge hemoglobin content, have been assumed to metabolize large quantities of NO. More recently, however, RBCs have been identified to reversibly bind, transport, and release NO within the cardiovascular system. We now provide evidence that RBCs from humans express an active and functional endothelial-type NOS (eNOS), which is localized in the plasma membrane and the cytoplasm of RBCs. This NOS is regulated by its substrate L-arginine, by calcium, and by phosphorylation via PI3 kinase. RBC-NOS activity regulates deformability of RBC membrane and inhibits activation of platelets. The NOS-dependent conversion of L-arginine in RBCs is comparable to that of cultured human endothelial cells. RBCs in eNOS-/- mice in contrast to wild-type mice lack NOS protein and activity, strengthening the evidence of an eNOS in RBCs. These data show an eNOS-like protein and activity in RBCs serving regulatory functions in RBCs and platelets, which may stimulate new approaches in the treatment of NO deficiency states inherent to several vascular and hematologic diseases.
Kleinbongard
Petra
P
Department of Medicine, Medical Clinic I, University Hospital RTWH Aachen, Pauwelsstrasse 30 D-52074 Aachen, Germany.
Schulz
Rainer
R
Rassaf
Tienush
T
Lauer
Thomas
T
Dejam
André
A
Jax
Thomas
T
Kumara
Intan
I
Gharini
Putrika
P
Kabanova
Svetlana
S
Ozüyaman
Burcin
B
Schnürch
Hans-Georg
HG
Gödecke
Axel
A
Weber
Artur-A
AA
Robenek
Mirko
M
Robenek
Horst
H
Bloch
Wilhelm
W
Rösen
Peter
P
Kelm
Malte
M
D001483:Base Sequence; D002462:Cell Membrane / Q000201:enzymology; D017931:DNA Primers; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values
D017931:DNA Primers; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III