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Dual effect of nitrogen dioxide on rat alveolar macrophage arachidonate metabolism

Journal Article · · Experimental Lung Research; (United States)
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Significant deficits in alveolar macrophage (AM) function have been associated with acute exposure to nitrogen dioxide (NO[sub 2]. The present investigation examined changes in enzymatic production of arachidonate metabolites from rat AM exposed to NO[sub 2]. While in vitro exposure of AM to NO[sub 2] concentrations between 0.1 and 5 ppm alone had small effects on basal synthesis of cyclooxygenase or lipoxygenase products, exposure to either 1 ppm (2 or 4 h) or 5 ppm (1h) markedly enhanced the response of AM to stimulation by the calcium ionophore, A23187. This pre-exposure led to significant increases in thromboxane A[sub 2], and 12-hydroxheptadecatrienoic acid (12-HHT)) and lipoxygenase products (leukotriene B (LTB[sub 4]) and monohydroxyeicosatetraenoate isomers) in response to A23187. In contrast, a 1-h exposure to 20 ppm NO[sub 2] alone significantly increased AM synthesis of thromboxane and 12-HHT, but suppressed the effect of subsequently added A23187. Increased synthesis of cyclooxygenase products with 20 ppm NO[sub 2] alone were blocked with the phospholipase inhibitor mepacrine and the cyclooxygenase inhibitor indomethacin. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) significantly reduced release of arachidonate; however, levels of thromboxane and 12 HHT were significantly increased. The results suggest a dual effect of NO[sub 2] on AM arachidonate metabolism in which low concentrations of NO[sub 2] had small effects on basal metabolism but markedly amplified the response to stimuli, while a high concentration of NO[sub 2] did the reverse. Such a complex dose-response effect may have significant impact in explaining the pathologic effects of NO[sub 2]. 33 refs., 7 figs., 1 tab.

OSTI ID:
6656532
Journal Information:
Experimental Lung Research; (United States), Journal Name: Experimental Lung Research; (United States) Vol. 19:1; ISSN EXLRDA; ISSN 0190-2148
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ALKALINE EARTH METALS
ANIMAL CELLS
ARACHIDONIC ACID
BASAL METABOLISM
CALCIUM
CARBOXYLIC ACIDS
CHALCOGENIDES
CONNECTIVE TISSUE CELLS
ELEMENTS
ENZYMES
IN VITRO
ISOMERS
LEVELS
MACROPHAGES
METABOLISM
METABOLITES
METALS
MONOCARBOXYLIC ACIDS
NITROGEN COMPOUNDS
NITROGEN DIOXIDE
NITROGEN OXIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
OXYGENASES
PHAGOCYTES
PRODUCTION
PROTEINS
SOMATIC CELLS
STIMULATION
STIMULI
SYNTHESIS