8-ISO-PGF2alpha production by alveolar macrophages exposed to hyperoxia.
Oxygen exposure for a sufficient duration at high partial pressure results in pulmonary edema in humans and animals. Although the specific mediators of oxygen toxicity are unknown, evidence suggests that oxygen-based radicals such as superoxide anion (O2.) are increased in the lungs in the presence of hyperoxia and contribute to this injury. A series of isomeric prostanoid compounds, the isoprostanes, are formed by the free radical-initiated lipid peroxidation of arachidonic acid (AA). One of these isomers, 8-iso-PGF2alpha, is elevated in the bronchial alveolar lavage fluid of rats exposed to 90% oxygen for 48 h and is associated with a significant increase in protein accumulation in the pulmonary extravascular space. Alveolar macrophages (AMs) are capable of producing large quantities of (O2.), suggesting a role in pulmonary oxygen toxicity. We hypothesized that isolated rat AMs exposed to hyperoxia generate increased amount of 8-iso-PGF2alpha. AMs were exposed to air or 90% oxygen for 6, 12, 24, 48, 72, 96, and 120 h in the absence and presence of AA and/or calcium ionophore (A23187) and 8-iso-PGF2alpha was measured in the culture media. Exposure of primary cultures of AMs to 90% oxygen resulted in a significant increase in 8-iso-PGF2alpha in the media (25 +/- 2 pg/mL) compared with air-exposed controls (14 +/- 1 pg/mL). The addition of 10 microM AA and 2 microM A23187 to the culture media resulted in a marked increase in 8-iso-PGF2alpha production by AMs exposed to air and 90% oxygen. However, treatment of AMs with the combination of AA and A23187, followed by exposure to 90% oxygen for 72 h, resulted in a 27-fold increase in 8-iso-PGF2alpha compared with media alone and 90% oxygen. AMs metabolized free and phospholipid-bound AA to 8-iso-PGF2alpha, an activity enhanced in the 90% oxygen environment. Finally, acetylsalicylic acid, a cyclooxygenase inhibitor and free radical scavenger, reduced but did not abolish production of 8-iso-PGF2alpha. This study provides evidence that AMs produce a free radical-mediated isomeric prostaglandin compound that may be involved in pulmonary oxygen toxicity.
Vacchiano
C A
CA
Department of Physiology, Medical University of South Carolina, Charleston 29425, USA.
Osborne
G R
GR
Tempel
G E
GE
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000096:biosynthesis; D028441:F2-Isoprostanes; D018496:Hyperoxia; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000633:toxicity; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
D028441:F2-Isoprostanes; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D016718:Arachidonic Acid; D000001:Calcimycin; D015237:Dinoprost; D010100:Oxygen