Depression of stimulated arachidonate metabolism and superoxide production in rat alveolar macrophages following in vivo exposure to 0. 5 ppm NO[sub 2]

Journal Article · Fri Jan 01 00:00:00 EST 1993 · Journal of Toxicology and Environmental Health; (United States)

OSTI ID:6465593

Robison, T W; Murphy, J K; Beyer, L L; Richters, A; Forman, H J ^[1]

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1. Childrens Hospital, Los Angeles, CA (United States) Univ. of Southern California, Los Angeles (United States)

Alveolar macrophages (AM) have been found to suffer significant functional deficits in response to nitrogen dioxide (NO[sub 2]) exposure. The present investigation examined changes in the activation of AM arachidonate metabolism and superoxide production in response to an environmentally relevant level of NO[sub 2]. Rats were exposed to 0.5 ppm NO[sub 2] for periods of 0.5-10 d and AM were obtained by bronchoalveolar lavage (BAL). NO[sub 2] exposure produced complex effects upon both unstimulated and stimulated AM arachidonate metabolism. Unstimulated AM synthesis of leukotriene B[sub 4] (LTB[sub 4]) was depressed rapidly within 1 d of exposure, and depressed again at 5 d. Alveolar macrophage production of thromboxane B[sub 2] (TxB[sub 2]), LTB[sub 4], and 5-hydroxyeicosatetraenoate (5-HETE) in response to stimulation with the calcium ionophore, A23187, were acutely depressed within 1 d of exposure; however, generation of these compounds recovered to air-control levels with longer exposure, while 5-HETE was increased at 10 d. AM production of LTB[sub 4] in response to zymosan-activated rat serum (ZAS), was not depressed until following 5 d of exposure and remained slightly lower than air-control levels at 10 d. Levels of TxB[sub 2], LTB[sub 4], prostaglandin E[sub 2] (PGE[sub 2]), and prostaglandin F[sub 2[alpha]] (PGF[sub 2[alpha]]) measured in BAL fluid (BALF) were found to be depressed within 4 h of exposure, suggesting an acute decrease in the in vivo pulmonary arachidonate metabolism; however, production of these compounds generally recovered to air-control levels with longer exposure. The AM superoxide production stimulated by phorbol myristate acetate (PMA) was decreased rapidly and continuously throughout the study. Thus, exposure to a low concentration of NO[sub 2] acutely depresses activation of AM arachidonate metabolism and superoxide production in response to external stimuli, and may impede defense against pulmonary infection. 14 refs., 5 figs., 1 tab.

• OSTI ID: 6465593
• Journal Information: Journal of Toxicology and Environmental Health; (United States), Vol. 38:3; ISSN 0098-4108
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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TIME DEPENDENCE
NITROGEN DIOXIDE
BIOLOGICAL EFFECTS
CHRONIC EXPOSURE
RATS
LUNGS
BAL
IN VIVO
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ANIMALS
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NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PHAGOCYTES
RADIOPROTECTIVE SUBSTANCES
REAGENTS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
THIOLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
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