Effects of short-term nitrogen monoxide inhalation on leukocyte adhesion molecules, generation of reactive oxygen species, and cytokine release in human blood.
Increased nitrogen monoxide (NO) concentrations change leukocyte function under a multitude of experimental conditions. NO inhalation is an experimental treatment for lung failure and exposes leukocytes to increased NO concentrations during passage through the lungs. To investigate whether short-term NO inhalation induces lasting changes in the function of circulating human leukocytes, venous blood samples were drawn from eight healthy male volunteers before and at the end of a 35-min period of breathing 40 ppm NO in 30% O(2). The leukocytes in the samples were subsequently analyzed for NO-induced changes in expression of cell surface molecules, generation of reactive oxygen species (ROS), and cytokine production by flow cytometry and ELISA techniques. The results were (1) NO inhalation changed neither the baseline nor the Escherichia coli lipopolysaccharide (LPS)-induced expression of the cell adhesion molecules CD11a, CD11b, CD11c, and CD62L (l-selectin) on neutrophilic granulocytes (PMN) or monocytes (Mo). The expression of CD14 and HLA-DR was also unchanged. (2) The generation of ROS in response to activation with phorbol myristate acetate increased in PMN after NO inhalation; an increase in Mo did not reach significance. (3) Baseline and LPS-stimulated production of IL-1beta decreased after NO inhalation, while the LPS-stimulated production of TNF-alpha increased. No changes in IL-6 production were detected.
Opdahl
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Department of Intensive Care, Ullevål University Hospital, Oslo, Norway.
Haugen
T
T
Hagberg
I A
IA
Aspelin
T
T
Lyberg
T
T
D000280:Administration, Inhalation; D000328:Adult; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D008706:Methemoglobin