CHARACTERIZATION OF PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE IN HUMAN BRONCHOALVEOLAR LAVAGE

Platelet-activating factor (PAF) is a mediator produced in human airwa ys during acute and chronic inflammatory lung diseases, The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PA F to lyso-PAF. To determine whether AH was present in human bronchoalv eolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild branchial asthma (n = 15) or with l ung fibrosis (n = 15), AH activity was consistently found in the cell- free BAL fluid. BAL-AH is an enzyme different from secretary phospholi pase A(2) and from plasma AH and erythrocyte AH, Furthermore, BAL-AH i s inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlate d with the number of BAL macrophages (r(s) = 0.63; p < 0.02). In addit ion, BAL macrophages release An both spontaneously and after stimulati on with tumor necrosis factor-alpha (TNF-alpha) (100 ng/ml). BAL-AH ac tivity in patients with bronchial asthma (1.32 +/- 0.18 pmol of PAF co nverted to lyso-PAF/min) is significantly lower than that in normal do nors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 +/- 0.87 pmol/min) is higher tha n that found in normal donors (p < 0.01). The variations in BAL-AH act ivity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active mo lecules rather than to changes in enzyme affinity, These data demonstr ate that human BAL fluid contains an extracellular AH activity that in activates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage, The secretion and inactivation of BAL-AH may influence the levels of t his enzyme in BAL fluid during acute and chronic inflammatory lung dis eases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.