Linoleic acid esterified in low density lipoprotein serves as substrate for increased arachidonic acid synthesis in differentiating monocytic cells.
The cellular metabolism of albumin- and lipoprotein-bound 18:2(n - 6) during monocytic differentiation was examined in the human premonocytic U937 and Mono Mac 6 cells. Differentiation for 72 h of U937 cells with retinoic acid (RA, 1 microM) or 1,25-(OH)2-vitamin D3 (1,25-D3, 10 nM) and of Mono Mac 6 cells with RA (1 microM) or lipopolysaccharide (LPS, 10 ng/ml) increased the desaturation and elongation of [1-14C]18:2(n - 6) to [1-14C]20:4(n - 6). In undifferentiated U937 and Mono Mac 6 cells, incubations with human LDL (100 micrograms/ml, 18 h) resulted in a 2.5-fold increase in 18:2(n - 6) levels in the cellular phospholipids. Differentiation of U937 cells with RA or or of Mono Mac 6 cells with LPS prior to LDL addition. Significantly reduced 18:2(n - 6) and elevated 20:4(n - 6) levels in cellular phospholipids. This increase in 20:4(n - 6) was likely not due to an increased incorporation of preformed 20:4(n - 6) esterified in LDL, as the receptor-specific degradation of [125I]LDL was reduced in both the RA-treated U937 and LPS-treated Mono Mac 6 cells. In U937 cells incubated with [1-14C]18:2(n - 6), the synthesis of TXB2, PGE2 and HHT could be detected after differentiation with RA. suggesting the availability of [1-14C]20:4(n - 6), derived from [1-14C]18:2(n - 6), for cyclooxygenase metabolism. Our results show that the conversion of 18:2(n - 6) to 20:4(n - 6) increases during monocyte differentiation. The 18:2(n - 6) supplied to the cells via the receptor-mediated uptake of LDL was utilized as substrate for the increased 20:4(n - 6) synthesis.
Hrboticky
N
N
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Müncher, Germany.
Sellmayer
A
A
Yeo
Y
Y
Pietsch
A
A
Weber
P C
PC
D016718:Arachidonic Acid / Q000096:biosynthesis*; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D004951:Esterification; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D005227:Fatty Acids; D008041:Linoleic Acids; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D000001:Calcimycin; D013929:Thromboxane B2; D014212:Tretinoin; D019787:Linoleic Acid; D002117:Calcitriol; D015232:Dinoprostone