EXCRETION OF PLATELET-ACTIVATING FACTOR-ACETYLHYDROLASE AND PHOSPHOLIPASE A(2) INTO NASAL FLUIDS AFTER ALLERGENIC CHALLENGE - POSSIBLE ROLEIN THE REGULATION OF PLATELET-ACTIVATING-FACTOR RELEASE

Platelet activating factor (PAF), a proinflammatory mediator synthesiz ed through a phospholipase A(2) (PLA(2))-dependent reaction, is hydrol yzed into its inactive metabolite, lyso-PAF; by a specific acetylhydro lase. Previous studies have shown that allergen challenge of patients with allergic rhinitis leads to an incr ease of the concentrations of lyso-PAF in nasal lavage fluid (NLF), whereas PAF is detected only mar ginally. PAF-hydrolyzing enzymes are expected to be released on allerg enic challenge, to account for the reduced concentrations of PAF in NL F. Here, we show that allergen challenge of patients with allergic rhi nitis; induces an increase of acetylhydrolase-like activity in NLF; wh ich peaks: within 10 minutes and returns to basal values 1 hour later. Acetyhydrolase hydrolyzed exogenous PAF with a complete loss of its a bility to induce platelet aggr egation. Allergen challenge also led to a parallel release of a PLA(2) in nasal fluids. This enzyme preferent ially hydrolyzes negatively char ged phospholipids (phosphatidic acid monomethyl ester and phosphatidylgylcerol) versus phosphatidylcholine. More interestingly the hydrolysis of phosphatidic acid monomethyl est er and phosphatidylglycerol by NLF was completely abolished by the add ition of ethylenediaminetetraacetic acid which had no effect on the hy drolysis of PAF; indicating that the PLA(2) secreted in nasal fluids i s not involved in the degradation of PAF. Finally, our results show th at allergen-induced increase in the concentrations of lyso-PAF and pro staglandin D-2 occurred with a kinetic similar to that of tosyl-L-argi nine-methyl-ester esterase, suggesting that mast cells are implicated in this process. Although no direct relationship was demonstrated betw een the absence of PAF and the increase of acetylhydrolase levels in N LF we suggest a potential role for this enzyme in the inactivation of PAF if the latter is released in the nasal lumen.