Acetyl-CoA:lyso-platelet-activating factor acetyltransferase activity in neutrophils from asthmatic patients and normal subjects

1. Platelet-activating factor is a putative mediator of inflammation in asthma and the enzyme acetyl-CoA:lyso-platelet-activating factor acetyltransferase appears to be important in regulating platelet-activating factor production by leucocytes. To determine whether there are differences in acetyl-transferase activity between asthmatic patients and normal subjects, enzyme activity was assayed in neutrophil lysates from atopic asthmatic patients (n = 20), aspirin-sensitive asthmatic patients (n = 12) and healthy, non-atopic, non-asthmatic control subjects (n = 20), both basally and after stimulation with the calcium ionophore A23187. 2. For a range of acetyl-CoA concentrations, acetyl-transferase activity (nmol of [acetyl-3H]PAF min−1 mg−1 of protein) in unstimulated neutrophils from atopic asthmatic patients was significantly higher than that for normal subjects (P = 0.038) and the mean Vmax. for atopic asthmatic patients [18.4 (SD 6.9) nmol min−1 mg−1 of protein] was significantly greater than that for the control subjects [14.9 (SD 4.6) nmol min−1 mg−1 of protein P 3. The mean ratio Vmax. stimulated/ Vmax. unstimulated for acetyltransferase from atopic asthmatic patients (1.71, SD 0.45) was significantly less than that for the normal subjects (2.13, SD 0.63, P 4. Vmax. stimulated was significantly correlated with Vmax. unstimulated in atopic asthmatic patients (P = 0.0001) and aspirin-sensitive asthmatic patients (P = 0.012), but not in normal subjects (P = 0.071). 5. These results suggest that, in atopic asthmatic patients, neutrophils may be subject to chronic priming in vivo for increased acetyltransferase activity and capacity for platelet-activating factor synthesis. In these patients the increased platelet-activating factor production may be contributing significantly to the degree of inflammation associated with their asthma.