NASAL ALLERGEN CHALLENGE GENERATES 1-0-HEXADECYL-2-LYSO-SN-GLYCERO-3-PHOSPHOCHOLINE

We studied antigen-induced platelet activating factor and the 1-0-hexa decyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF) in nasal lavage fl uids (NLF) by combined gas chromatography/mass spectrometric analysis (GC/MS). During the early allergic reaction, there was a dramatic incr ease in the levels of lyso-PAF that peaked at 15 min (2.6 +/- 5.2 ng/m l, mean +/- SEM, n = 6). increasing doses of antigen produced a dose-d ependent increase in the levels of lyso-PAF that peaked at the highest dose. Levels of lyso-PAF correlated strongly with those of N-alpha-to syl-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 signific ant increase in the quantity of lyso-PAF found in NLF from allergic in dividuals challenged with diluent or nonallergic individuals challenge d with antigen. In subjects showing a late phase reaction, as indicate d by symptoms and histamine release, we detected lyso-PAF along with T AME-esterase activity and histamine during the late phase reaction. In contrast to lyso-PAF, PAF levels were near or below the detection lim it of the assay in NLF and remained unchanged after antigen challenge. We also investigated the potential pathways for lyso-PAF generation f rom e-acetylated phospholipids. We found that the time required for de acetylation of 50% of [H-3]PAF (t1/2) to lyso-PAF was 50 min in baseli ne secretions and 10 and 22 min in NLF obtained 10 min and 24 h after antigen challenge, respectively. These data suggested that catabolic p athways were present in NLF. One catabolic pathway for PAF found to be present in NLF included relatively high levels of phospholipase A(2) (PLA(2)) activity. PLA(2) activity increased in NLF in subjects challe nged with histamine. Our data indicate that lyso-PAF levels are elevat ed during the early and late reaction after antigen challenge. These i ncreased levels may result, in part, from rapid deacetylation of 2-ace tylated phospholipids or from PLA(2)-mediated hydrolysis of phospholip ids in NLF Lyso-PAF and other lysophospholipids that may be produced d uring antigen challenge may act as membrane perturbing agents or subst rates for biologically active compounds, thereby having an important r ole in allergic and other forms of rhinitis.