Platelet activating factor (PAF), a proinflammatory mediator synthesized through a
phospholipase A2 (PLA2)-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 increase 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. Acetylhydrolase hydrolyzed exogenous PAF with a complete loss of its ability to induce platelet aggregation.
Allergen challenge also led to a parallel release of a PLA2 in nasal fluids. This
enzyme preferentially hydrolyzes negatively charged
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 PLA2 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 D2 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.