title: Red blood cells express a functional endothelial nitric oxide synthase.
abstract: 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.
authors.affiliation: Department of Medicine, Medical Clinic I, University Hospital RTWH Aachen, Pauwelsstrasse 30 D-52074 Aachen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.forename: Thomas
authors.initials: T
authors.lastname: Lauer
authors.forename: André
authors.initials: A
authors.lastname: Dejam
authors.forename: Thomas
authors.initials: T
authors.lastname: Jax
authors.forename: Intan
authors.initials: I
authors.lastname: Kumara
authors.forename: Putrika
authors.initials: P
authors.lastname: Gharini
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kabanova
authors.forename: Burcin
authors.initials: B
authors.lastname: Ozüyaman
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schnürch
authors.forename: Axel
authors.initials: A
authors.lastname: Gödecke
authors.forename: Artur-A
authors.initials: AA
authors.lastname: Weber
authors.forename: Mirko
authors.initials: M
authors.lastname: Robenek
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Peter
authors.initials: P
authors.lastname: Rösen
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: 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
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III