Identification of lipoxin A₄ and its relationship to the sulfidopeptide leukotrienes C₄, D₄, and E₄ in the bronchoalveolar lavage fluids obtained from patients with selected pulmonary diseases

Lipoxins are biologically active trihydroxytetraene containing products derived from arachidonic acid that are formed by interactions between lipoxygenases. Although the lipoxins have been generated from mixed cell suspensions in vitro, it has not been established whether these products are synthesized in vivo. We have performed bronchoalveolar lavage (BAL) in 12 patients with lung disease (sarcoid, six; pneumonia, two; asthma, two; carcinoma, one; alveolitis of unknown cause, one) and in six normal control subjects. The BAL fluid was analyzed for lipoxin A₄ (LXA₄) using gas chromatography mass spectrometry with selective ion monitoring, and the levels of the sulfidopeptide leukotrienes were determined using reverse-phase high-performance liquid chromatography and radioimmunoassay. LXA₄ was detected in BAL fluid from nine of the 12 patients studied. The levels of LXA₄ ranged from 0.4 to 2.8 ng/ml. LXA₄ was not detected in any of the six normal subjects. Sulfidopeptide leukotrienes were detected in all the BAL samples, ranging from 0.04 to 0.7 ng/ml, and there was no significant difference between the patients and the normal subjects. In patients with detectable LXA₄ in BAL fluid, the ratio of the concentrations of LXA₄ to those of the sulfidopeptide leukotrienes ranged from 1.9 to 62 (mean, 19.0). This is the first demonstration of the presence of LXA₄ in disease.