The activities of monocyte lysophosphatidylcholine acyltransferase and coenzyme A-independent transacylase are changed by the inflammatory cytokines tumor necrosis factor alpha and interferon gamma.
Alteration of membrane phospholipid fatty acid compositions has been shown to be important for leukocyte inflammatory responses. Such modification of the molecular species of these lipid classes requires deacylation and reacylation reactions and for phosphatidylcholines, lysophosphatidylcholine acyltransferase (LPCAT) and a coenzyme A-independent transacylase (CoAIT) can each be involved. Since previous studies have shown a significant IFNgamma- and TNFalpha-induced modification of phosphatidylcholine species, we have examined whether these inflammatory cytokines alter the activity of reacylation enzymes in the human monocyte cell line MonoMac 6 (MM6). IFN-gamma caused a significant increase in the activity of the LPCAT and CoAIT enzymes in the microsomal fraction at concentrations and over a time-course consistent with an important role for these enzymes in the sensitization (priming) of monocytes. In contrast, TNFalpha was found to significantly increase the activity of the CoAIT by 50% over controls in MM6 cells after 30 min incubation with the cytokine, but decreased LPCAT activity by 65% after 24 h incubation. Such data imply that CoAIT is important for the remodelling of phospholipid composition, which is seen during the acute response of cells to TNFalpha. The results provide further information to emphasise the role of acyltransferases as part of the molecular mechanism underlying inflammation.
Neville
Nicola T
NT
School of Biosciences, Cardiff University, Wales, UK.
Parton
Joan
J
Harwood
John L
JL
Jackson
Simon K
SK
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D000217:Acyltransferases / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000217:Acyltransferases; C039766:arachidonyl transacylase; D008243:1-Acylglycerophosphocholine O-Acyltransferase