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 lysophospholipids. AA, in turn, serves as a substrate for the synthesis of leukotrienes which can cause bronchoconstriction and airways edema and appear to be important mediators of clinical asthma. Further, lysophospholipids may be cytotoxic and/or impair the function of surfactant. We examined the release of secretory PLA(2) (sPLA(2)) and AA into the airways after antigen challenge in 16 subjects with allergic asthma. Asthmatic subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) before 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 between normal and asthmatic subjects in either BAL fluid (BALF) sPLA(2) activity or AA concentration at baseline. Both sPLA(2) and AA increased after antigen challenge (p < 0.01 and 0.05, respectively). These changes 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.