PHOSPHOLIPASE A(2) AND ARACHIDONATE INCREASE IN BRONCHOALVEOLAR LAVAGE FLUID AFTER INHALED ANTIGEN CHALLENGE IN ASTHMATICS

Phospholipases A(2) (PLA(2)) hydrolyze phospholipids resulting in the release of fatty acids including arachidonic acid (AA) and lysophospho lipids. AA, in turn, serves as a substrate for the synthesis of leukot rienes which can cause bronchoconstriction and airways edema and appea r to be important mediators of clinical asthma. Further, lysophospholi pids may be cytotoxic and/or impair the function of surfactant. We exa mined the release of secretory PLA(2) (sPLA(2)) and AA into the airway s after antigen challenge in 16 subjects with allergic asthma. Asthmat ic subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) b efore and after inhaled antigen challenge; in addition, a single BAL, without inhaled antigen, was performed in 10 control subjects. BAL was obtained at 4 h (n = 7), the time of the late asthmatic response (LAR ) (n = 5), or 24 h (n = 4) after challenge. There was no difference be tween normal and asthmatic subjects in either BAL fluid (BALF) sPLA(2) activity or AA concentration at baseline. Both sPLA(2) and AA increas ed after antigen challenge (p < 0.01 and 0.05, respectively). These ch anges were most marked 4 h after challenge (p < 0.03 for both). sPLA(2 ) may play an important role in the generation of AA in patients with asthma.