ACETYL-COA LYSO-PLATELET-ACTIVATING-FACTOR ACETYLTRANSFERASE ACTIVITYIN NEUTROPHILS FROM ASTHMATIC-PATIENTS AND NORMAL SUBJECTS

1. Platelet-activating factor is a putative mediator of inflammation i n asthma and the enzyme acetyl-CoA : lyso-platelet-activating factor a cetyltransferase appears to be important in regulating platelet-activa ting factor production by leucocytes. To determine whether there are d ifferences in acetyltransferase activity between asthmatic patients an d normal subjects, enzyme activity was assayed in neutrophil lysates f rom atopic asthmatic patients (n=20), aspirin-sensitive asthmatic pati ents (n=12) and healthy, non-atopic, non-asthmatic control subjects (n =20), both basally and after stimulation with the calcium ionophore A2 3187. 2. For a range of acetyl-CoA concentrations, acetyl-transferase activity (nmol of [acetyl-H-3]PAF min-1 mg-1 of protein) in unstimulat ed neutrophils from atopic asthmatic patients was significantly higher than that for normal subjects (P=0.038) and the mean V(max) for atopi c asthmatic patients [18.4 (SD 6.9)nmol min-1 mg-1 of protein] was sig nificantly greater than that for the control subjects [14.9(SD 4.6)nmo l min-1 mg-1 of protein P<0.05]. The mean V(max) for aspirin-sensitive asthmatic patients [15.9 (SD 6.9) nmol min-1 mg-1 of protein] was not significantly different from that for the normal subjects. 3. The mea n ratio V(max) stimulated/V(max) unstimulated for acetyltransferase fr om atopic asthmatic patients (1.71, SD 0.45) was significantly less th an that for the normal subjects (2.13, SD 0.63, P<0.05), suggesting th at acetyltransferase from atopic asthmatic patients was less sensitive to stimulation with A23187 in vitro. The mean ratio V(max). stimulate d/ V(max) unstimulated for aspirin-sensitive asthmatic patients (2.05, SD 0.71) was not significantly different from that for the normal sub jects. 4. V(max) stimulated was significantly correlated with V(max) u nstimulated in atopic asthmatic patients (P=0.0001) and aspirin-sensit ive asthmatic patients (P=0.012), but not in normal subjects (P=0.071) . 5. These results suggest that, in atopic asthmatic patients, neutrop hils may be subject to chronic priming in vivo for increased acetyltra nsferase activity and capacity for platelet-activating factor synthesi s. In these patients the increased platelet-activating factor producti on may be contributing significantly to the degree of inflammation ass ociated with their asthma.