Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis.
The pathogenesis of oxygen toxicity remains unknown but may involve leukocyte mediated injury. The effects of hyperoxia on several lower respiratory tract parameters were examined in bronchoalveolar lavage fluid of normal nonsmoking subjects who inhaled a fractional inspired oxygen concentration of 50 percent (mean exposure: 44 h). Evidence that 50 percent O2 produced oxidative stress in the lung included recovery of fluorescent products of lipid peroxidation and partial oxidation of alpha 1-antitrypsin in BAL fluid obtained after O2 exposure. To examine whether alveolar macrophage-derived leukotriene B4 may be generated in response to 50 percent O2, AM were isolated from O2-exposed subjects and compared with AM recovered from subjects breathing room air. Leukotriene B4 levels were elevated in supernatants from both unstimulated and arachidonic acid-stimulated AM obtained from hyperoxia-exposed subjects. In hyperoxia-exposed individuals, LTB4 levels were also elevated in extracted BAL fluid. The percentage of BAL neutrophils was also significantly increased after O2 exposure (2.8 +/- 0.6 vs 1.2 +/- 0.4 percent, p = 0.05). We conclude that an FIO2 of 50 percent inhaled for 44 h is associated with enhanced oxidative stress, stimulation of AM to release LTB4, and a small but significantly increased percentage of neutrophils recovered in BAL fluid.
Griffith
D E
DE
Department of Medicine, University of Texas Health Center, Tyler 75710.
Garcia
J G
JG
James
H L
HL
Callahan
K S
KS
Iriana
S
S
Holiday
D
D
D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000032:analysis; D016718:Arachidonic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007975:Leukotriene B4 / Q000096:biosynthesis*; D015227:Lipid Peroxidation; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000502:physiology*
D000418:Albumins; D007074:Immunoglobulin G; D007975:Leukotriene B4; D016718:Arachidonic Acid; D010100:Oxygen