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

Platelet activating factor (PAF), a proinflammatory mediator synthesized through a phospholipase A(2) (PLA(2))-dependent reaction, is hydrolyzed into its inactive metabolite, lyso-PAF; by a specific acetylhydrolase. 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 marginally. PAF-hydrolyzing enzymes are expected to be released on allergenic challenge, to account for the reduced concentrations of PAF in NLF. Here, we show that allergen challenge of patients with allergic rhinitis; induces an increase of acetylhydrolase-like activity in NLF; which peaks: within 10 minutes and returns to basal values 1 hour later. Acetyhydrolase hydrolyzed exogenous PAF with a complete loss of its ability to induce platelet aggr egation. Allergen challenge also led to a parallel release of a PLA(2) in nasal fluids. This enzyme preferentially hydrolyzes negatively char ged phospholipids (phosphatidic acid monomethyl ester and phosphatidylgylcerol) versus phosphatidylcholine. More interestingly the hydrolysis of phosphatidic acid monomethyl ester and phosphatidylglycerol by NLF was completely abolished by the addition of ethylenediaminetetraacetic acid which had no effect on the hydrolysis of PAF; indicating that the PLA(2) secreted in nasal fluids is not involved in the degradation of PAF. Finally, our results show that allergen-induced increase in the concentrations of lyso-PAF and prostaglandin D-2 occurred with a kinetic similar to that of tosyl-L-arginine-methyl-ester esterase, suggesting that mast cells are implicated in this process. Although no direct relationship was demonstrated between the absence of PAF and the increase of acetylhydrolase levels in NLF we suggest a potential role for this enzyme in the inactivation of PAF if the latter is released in the nasal lumen.