Effects of ozone exposure on lipid metabolism in human alveolar macrophages.
Alveolar macrophages (AM) store arachidonic acid (AA), which is esterified in cellular phospholipids until liberated by phospholipase A2 or C after exposure to inflammatory stimuli. After release, there can be subsequent metabolism of AA into various potent, biologically active mediators including prostaglandins and platelet-activating factor (PAF). To examine the possibility that these mediators may account for some of the pathophysiologic alterations seen in the lung after ozone (O3) exposure, human AM were collected by bronchoalveolar lavage of normal subjects, plated into tissue culture dishes, and the adherent cells were incubated with [3H]AA or [3H]lysoPAF. Human AM exposed to 1.0 ppm O3 for 2 hr released 65 +/- 12% more tritium, derived from [3H]AA, than paired, air-exposed controls into media supernatants. In other studies using a similar O3 exposure protocol, there was also a significant increase in human AM prostaglandin E2 production (2.0 +/- 0.5-fold increase above air-exposure values, p less than 0.01, n = 17). In additional studies, using a similar O3 exposure protocol (1.0 ppm for 1 hr), there was also a significant increase in human AM PAF content (1.7 +/- 0.2-fold increase above air-exposure values, p less than 0.02, n = 5). These potent lipid mediators, originally derived from human AM, may play an important role in the mechanisms of O3 lung toxicity.
Friedman
M
M
Department of Medicine and Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599.
Madden
M C
MC
Samet
J M
JM
Koren
H S
HS
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010126:Ozone / Q000009:adverse effects*; D010972:Platelet Activating Factor / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism
D010972:Platelet Activating Factor; D011453:Prostaglandins; D016718:Arachidonic Acid; D010126:Ozone