Nitric oxide blocks inflammatory cytokine secretion triggered by CD23 in monocytes from allergic, asthmatic patients and healthy controls.
BACKGROUND
In allergic asthma, monocytes/macrophages may be activated to produce inflammatory cytokines through triggering of the low-affinity IgE receptor (CD23). Elevated airway levels of nitric oxide (NO) are associated with asthmatic exacerbations. Our previous work suggested that NO may function in an anti-inflammatory capacity by downregulating endotoxin-stimulated cytokine production by alveolar macrophages and matured monocytes.


OBJECTIVE
The purpose of this study was to determine the effect of NO on CD23-triggered cytokine production by monocytes from asthmatic patients and healthy controls.


METHODS
Monocytes were obtained from normal volunteers (n = 13) and asthmatic patients with atopy (n = 8). Monocyte cultures were treated with interleukin-4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF) for 24 hours to upregulate CD23 expression. Cultures were stimulated by anti-CD23 and treated with DETA NONOate [2,2-(hydroxynitrosohydrazonon)-bis-ethanamine] releases NO in culture with t(1/2) of 20 hours at 37 degrees C for 24 hours. Cell free culture supernatants were collected and assayed by enzyme-linked immunoadsorbent assay for macrophage inflammatory protein-1-alpha (MIP-1) and IL-6.


RESULTS
NO inhibits MIP-1 secretion triggered by CD23 activation of IL-4- and GM-CSF-matured monocytes (percentage of MIP-1 suppression = 52 +/- 11 of monocytes from asthmatic patients; percentage = 55 +/- 8 healthy controls). The inhibitory effect of NO was not cytokine-specific, as similar results were obtained with IL-6 (50 +/- 9% IL-6 suppression, asthmatic patients; 66 +/- 20%, healthy controls).


CONCLUSIONS
The results demonstrate for the first time an inhibitory effect of NO on cytokine production stimulated by CD23 receptor activation. We suggest that NO may be upregulated as a potent anti-inflammatory agent in the asthmatic lung.
Wishah
Kholoud
K
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195-5038, USA.
Malur
Anagha
A
Raychaudhuri
Baisakhi
B
Melton
Alton L
AL
Kavuru
Mani S
MS
Thomassen
Mary Jane
MJ
D000328:Adult; D001249:Asthma / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D017455:Receptors, IgE / Q000032:analysis / Q000502:physiology*
D016207:Cytokines; D016328:NF-kappa B; D017455:Receptors, IgE; D015847:Interleukin-4; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor