Spontaneous oxygen radical production at sites of antigen challenge in allergic subjects.
Allergic reactions in the lung are characterized by the production of mediators, an influx of inflammatory cells, increased vascular permeability, and changes in airway mechanics. The mechanisms responsible for these airway changes have not been fully defined but may involve the production of reactive oxygen species (ROS) produced by the inflammatory cells. To examine whether ROS are produced by inflammatory cells at sites of antigen exposure, bronchoalveolar lavage (BAL) was performed in airway segments 19 h after challenge with saline or antigen in 14 allergic subjects. Antigen challenge increased cell recovery, predominantly as a result of an influx of eosinophils. Using electron paramagnetic resonance (EPR) spectroscopy with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), BAL cells from saline-challenged sites produced minimal ROS. Cells from antigen-challenged sites spontaneously produced a prominent DMPO-OH signal that was inhibited by superoxide dismutase (SOD), indicating the production of superoxide anions (O2-.). Reduction of ferricytochrome c and production of luminol-dependent chemiluminescence via SOD-inhibitable reactions confirmed the spontaneous production of O2-. Following density gradient separation of the antigen-challenged BAL cells, the granulocytic cells, which were predominantly eosinophils, not the mononuclear cells, were the major source of the ROS. At the sites of antigen challenge, the degree of airway permeability as assessed by albumin concentration in BAL fluid was correlated with O2- production by BAL cells measured by EPR spectroscopy. These results demonstrate that cells at sites of antigen challenge generate ROS that may contribute to the airway injury associated with allergic inflammation.
Sanders
S P
SP
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Zweier
J L
JL
Harrison
S J
SJ
Trush
M A
MA
Rembish
S J
SJ
Liu
M C
MC
D000328:Adult; D000485:Allergens; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003574:Cytochrome c Group / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000378:metabolism*; D012709:Serum Albumin / Q000032:analysis; D013481:Superoxides / Q000378:metabolism
D000485:Allergens; D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D013481:Superoxides; D008165:Luminol