Endothelial cell nitric oxide production in acute chest syndrome.
Acute chest syndrome (ACS) is the most common form of acute pulmonary disease associated with sickle cell disease. To investigate the possibility that alterations in endothelial cell (EC) production and metabolism of nitric oxide (NO) products might be contributory, we measured NO products from cultured pulmonary EC exposed to red blood cells and/or plasma from sickle cell patients during crisis. Exposure to plasma from patients with ACS caused a 5- to 10-fold increase in S-nitrosothiol (RSNO) and a 7- to 14-fold increase in total nitrogen oxide (NO(x)) production by both pulmonary arterial and microvascular EC. Increases occurred within 2 h of exposure to plasma in a concentration-dependent manner and were associated with increases in endothelial nitric oxide synthase (eNOS) protein and eNOS enzymatic activity, but not with changes in nitric oxide synthase (NOS) III or NOS II transcripts, inducible NOS (iNOS) protein nor iNOS enzymatic activity. RSNO and NO(x) increased whether plasma was obtained from patients with ACS or other forms of vasoocclusive crisis. Furthermore, an oxidative state occurred and oxidative metabolites of NO, particularly peroxynitrite, were produced. These findings suggest that altered NO production and metabolism to damaging oxidative molecules contribute to the pathogenesis of ACS.
Hammerman
S I
SI
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Klings
E S
ES
Hendra
K P
KP
Upchurch
G R
GR
Rishikof
D C
DC
Loscalzo
J
J
Farber
H W
HW
D000818:Animals; D001790:Blood Physiological Phenomena; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006450:Hemoglobin SC Disease / Q000150:complications*; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D008623:Mercaptoethanol; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D012333:RNA, Messenger; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione