Metabolism of Platelet Activating Factor (PAF) and Lyso-PAF in Polymorphonuclear Granulocytes from Severely Burned Patients

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Abstract
We studied the metabolism of 3H-pIatelet activating factor (PAF) and lyso-PAF in human polymorphonuclear granulocytes (PMN) from severely burned patients (n = 6) on days 1, 5, 9, 15, and 25 post-trauma. All patients suffered from a severe burn trauma of more than 30% total body surface area. Stimulation of PMN in healthy donors (n = 10) with the Ca-ionophore resulted in the conversion of 3H-lyso-PAF into PAF (18 ± 2% of total radioactivity) and alkyl-acyl-glycero-phosphorylcholine (alkyl-acyl-GPC, 50 ± 6%). In burned patients a significantly reduced formation of 3H-PAF was observed between days 1 and 15 post-trauma (day 9: 1 ± l%,p < 0.0001). This pattern was normalized again in patients (n = 5) who survived the trauma after septic periods and was observed during the second week post-trauma. In one patient who succumbed to his injuries a sustained inhibition of PAF formation was observed up to his death. The decreased formation of PAF correlated weakly with the appearance of immature granulocytes within the analyzed cell fraction (ratio of immature cells versus PAF-formation, r = –0.55, p = 0.02). In addition, the metabolism of 3H-PAF was inhibited after the burn trauma; granulocytes of healthy donors rapidly metabolized PAF into alkyl-acyl-GPC while the amounts of the intermediate lyso-PAF ranged below the detection limit; in contrast, in granulocytes from severely burned patients lyso-PAF was regularly detected (up to 16% of total radioactivity) and the inactivation of PAF was decreased (5-min incubation day 1, burned patients 95 ± 7% of PAF remains stable, versus 80 ± 5% in healthy donors, p < 0.001). Combined with previous data (21) which indicated a decreased formation of leukotriene B4, our studies provide evidence for a severe impairment of granulocytes to establish a chemotactic gradient via the generation of lipid mediators.

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