Nasal allergen challenge generates 1-0-hexadecyl-2-lyso-sn-glycero-3-phosphocholine

We studied antigen-induced platelet activating factor and the 1-0-hexadecyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF) in nasal lavage fluids (NLF) by combined gas chromatography/mass spectrometric analysis (GC/MS). During the early allergic reaction, there was a dramatic increase in the levels of lyso-PAF that peaked at 15 min (2.6 ± 5.2 ng/ml, mean ± SEM, n = 6). Increasing doses of antigen produced a dose-dependent increase in the levels of lyso-PAF that peaked at the highest dose. Levels of lyso-PAF correlated strongly with those of N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity (r_s = 0.82, p = 0.0001) and histamine (r_s = 0.57, p = 0.002). There was no significant increase in the quantity of lysoPAF found in NLF from allergic individuals challenged with diluent or nonallergic individuals challenged with antigen. In subjects showing a late phase reaction, as indicated by symptoms and histamine release, we detected lyso-PAF along with TAME-esterase activity and histamine during the late phase reaction. In contrast to lyso-PAF, PAF levels were near or below the detection limit of the assay in NLF and remained unchanged after antigen challenge. We also investigated the potential pathways for lyso-PAF generation from 2-acetylated phospholipids. We found that the time required for deacetylation of 50% of [³H]PAF (t1/2) to lyso-PAF was 50 min in baseline secretions and 10 and 22 min in NLF obtained 10 min and 24 h after antigen challenge, respectively. These data suggested that catabolic pathways were present in NLF. One catabolic pathway for PAF found to be present in NLF included relatively high levels of phospholipase A₂ (PLA₂) activity. PLA₂ activity increased in NLF in subjects challenged with histamine. Our data indicate that lyso-PAF levels are elevated during the early and late reaction after antigen challenge. These increased levels may result, in part, from rapid deacetylation of 2-acetylated phospholipids or from PLA₂-mediated hydrolysis of phospholipids in NLF. Lyso-PAF and other lysophospholipids that may be produced during antigen challenge may act as membrane perturbing agents or substrates for biologically active compounds, thereby having an important role in allergic and other forms of rhinitis.