Effect of alkyl-lysophospholipids on phosphatidylcholine biosynthesis in leukemic cell lines.

Alkyl-lysophospholipids are ether analogues of lysophospholipids that have tumoricidal activity mediated through activation of macrophages or by direct effect on tumor cells by disturbance of phospholipid metabolism. The effect of racemic 1-octadecyl-2-methyl-sn-glycero-3 phosphocholine on phosphatidylcholine synthesis was investigated in sensitive (HL-60) and resistant (K-562) human leukemic cell lines. Radiolabeled lysophosphatidyl-choline, choline, and methionine incorporation into phosphatidylcholine was measured in intact cells exposed for 24 h to varying concentrations of the compound. In HL-60 cells, marked inhibition of phosphatidylcholine synthesis was demonstrated using lysophosphatidylcholine or choline as precursors, but no effect was observed on methionine incorporation. No effects were observed in K-562 cells. These investigations suggest that alkyl-lysophospholipids inhibit phosphatidylcholine synthesis via the acyltransferase reaction and from choline, but not from methionine.

The effect of alkyl-lysophospholipids on tritiated thymidine incorporation and clonogenicity in vitro of normal and leukemic human cells.

Alkyl-lysophospholipids are analogues of 2-lysophosphatidylcholine which have been reported to have selective antitumor activity. A survey of the in vitro activity of racemic 1-octadecyl-2-methoxy-glycero-3 phosphorylcholine on in vitro clonogenicity in soft agar and tritiated thymidine incorporation was conducted on bone marrow specimens from a series of patients with acute myelogenous leukemia (AML) and chronic myelocytic leukemia (CML) and hematologically normal individuals. A dose- and time-dependent inhibition of colony formation and thymidine incorporation was observed in the normal and leukemic specimens. No selective effect of the compound could be demonstrated under the conditions employed in these studies.

Bacteria-immune system interactions. IX. Modulation of human and murine cytotoxic reactions by crude lipoteichoic acid extracted from Staphylococcus aureus.

Crude lipoteichoic acid extracts of Staphylococcus aureus (SA-LTA) or Bacillus glogigii (Bg-LTA) inhibited cytotoxic reactions when added at day 0 to human or murine mixed lymphocyte reactions (MLR). The inhibition was dose dependent, and at low Sa-LTA concentrations it did not require reduction of thymidine incorporation into effector lymphocytes. In the murine system, Sa-LTA was a much more potent inhibitor than Bg-LTA. LTAs of both origin also could inhibit cytotoxic reactions when bound to stimulator cells. However, the LTA derivatized stimulator cells were much more inhibitory in the human than in the murine MLR. The inhibition of human cytotoxic reaction by Sa-LTA derivatized stimulator was not associated with a significant reduction of thymidine incorporation in effector cells.

Bacteria-immune system interactions. VIII. Modulation of human cytotoxic reactions by crude lipoteichoic acid extracts of Bacillus globigii.

Crude lipoteichoic acid (LTA)1 extracts were prepared from Bacillus globigii (Bg-LTA). The addition of Bg-LTA to mixed lymphocyte reactions (MLR) produced a dose dependent inhibition of specific cytotoxic reactions and of tritiated thymidine (3H-TdR) incorporation. Much less Bg-LTA was needed to inhibit the initiation (addition at day 0) than the effector phase (addition at day 6) of the cytotoxic reactions. None of the LTA quantities used had a toxic effect on the lymphocytes. LTA pretreated stimulator cells also had a modulatory effect on the cytotoxic reactions. Stimulators pretreated with very low or very high LTA concentrations had no effect; however, pretreatment with intermediate concentrations induced a drastic inhibition of cytotoxicity. LTA pretreated stimulator cells did not significantly affect 3H-TdR incorporation. Suppression of the cytotoxic reaction could also be obtained by LTA-pretreatment of the effector cells.