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 premonocyti c U937 and Mono Mac 6 cells. Differentiation for 72 h of U937 cells wi th retinoic acid (RA, 1 mu M) or 1,25-(OH)(2)-vitamin D-3 (1,25-D-3, 1 0 nM) and of Mono Mac 6 cells with RA (1 mu M) or lipopolysaccharide ( LPS, 10 ng/ml) increased the desaturation and elongation of [1-C-14]18 :2(n - 6) to [1-C-14]20:4(n - 6). In undifferentiated U937 and Mono Ma c 6 cells, incubations with human LDL (100 mu g/ml, 18 h) resulted in a 2.5-fold increase in 18:2(n - 6) levels in the cellular phospholipid s. Differentiation of U937 cells with RA or or of Mono Mac 6 cells wit h LPS prior to LDL addition, significantly reduced 18:2(n - 6) and ele vated 20:4(n - 6) levels in cellular phospholipids. This increase in 2 0:4(n - 6) was likely not due to an increased incorporation of preform ed 20:4(n - 6) esterified in LDL, as the receptor-specific degradation of [I-125]LDL was reduced in both the RA-treated U937 and LPS-treated Mono Mac 6 cells. In U937 cells incubated with [1-C-14]18:2(n - 6), t he synthesis of TXB(2), PGE(2) and HHT could be detected after differe ntiation with RA, suggesting the availability of [1-C-14]20:4(n - 6), derived from [1-C-14]18:2(n - 6), for cyclooxygenase metabolism. Our r esults show that the conversion of 18:2(n - 6) to 20:4(n - 6) increase s during monocyte differentiation. The 18:2(n - 6) supplied to the cel ls via the receptor-mediated uptake of LDL was utilized as substrate f or the increased 20:4(n - 6) synthesis.