UTILIZATION OF INTRACELLULAR ACYLCARNITINE POOLS BY MONONUCLEAR PHAGOCYTES

Carnitine is essential for the metabolism of long-chain fatty acids an d has both direct and indirect roles in the metabolism of short-chain and medium-chain acyl-CoAs. The purpose of this study was to quantitat e and identify the individual acylcarnitines that occur in human monon uclear phagocytes (MNP) after activating them with phorbol-12-myristat e 13-acetate (PMA). Mononuclear phagocytes were isolated from healthy adults and the levels of free carnitine and individual acylcarnitines were determined in unactivated and activated cells. The degree of acti vation of MNP was assessed by following hydrogen peroxide production. In unactivated cells, acetyl-L-carnitine represented more than 80% of the total acylcarnitine pool. Small amounts of 3-carbon and 4-carbon a cylcarnitines were present, with less than 10% of the carnitine pool b eing long-chain acylcarnitine. Free carnitine in unactivated cells rep resented 7% of the total carnitine pool, which remained essentially un changed in unactivated cells when monitored for a period of 60 min. Ho wever, free carnitine rose to more than 50% of the total pool in PMA-a ctivated cells. Similarly, after 1 h of activation, the acetylcarnitin e level in activated cells decreased by more than 50%. These data sugg est that acetylcarnitine plays a key metabolic role as MNP initiate an immune response. It was further shown that MNP contain both carnitine acetyltransferase and malonyl-CoA-sensitive carnitine palmitoyltransf erase in mitochondrial-enriched fractions, as well as in post-mitochon drial supernatant fractions.