Metabolism of platelet-activating factor in human haematopoietic cell lines. Differences between myeloid and lymphoid cells

Abstract

The binding and metabolism of platelet-activating factor (PAF) was studied in human cell lines resembling myeloid cells (HL60 and U937) and B and T lymphocytes (Daudi and Jurkat). All of the cell lines were found to bind and catabolize exogenous [3H]PAF in a time- and temperature-dependent manner. PAF binding could also be demonstrated in isolated membrane fractions, which provides further evidence of the existence of true membrane receptors. Myeloid cell lines contained numbers of receptors at least 10-fold higher than in lymphoid cell lines. Biosynthesis of PAF upon challenge by ionophore A23187 could be demonstrated in HL60 and U937 cells. In contrast, lymphoid cell lines were unable to produce PAF. Incubation with [14C]acetate showed incorporation of the label into three main fractions: neutral lipids, phosphatidylcholine and PAF, but the distribution of the label varied depending on the cell line. Significant incorporation into phosphatidylcholine was observed in uninduced myeloid cell lines. A phospholipase A2 acting on 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine and an acetyl-CoA:lyso-PAF acetyltransferase were expressed in the HL60 cell line and showed variations in specific activity with granulocytic differentiation. In contrast, these enzyme activities were not expressed in Daudi and Jurkat cell lines. These data indicate (1) the occurrence of PAF binding and catabolism in both myeloid and lymphoid cell lines; (2) the restriction of PAF biosynthesis to myeloid cell lines, especially HL60 cells; (3) the occurrence of differentiation-elicited changes in the specific activities of the enzymes involved in PAF biosynthesis by the remodelling pathway; and (4) the central role played by the disposal of lyso-PAF, a product of the phospholipase A2 reaction, in PAF biosynthesis.

Platelet-Activating Factor Production in the Spinal Cord of Experimental Allergic Encephalomyelitis Mice via the Group IVA Cytosolic Phospholipase A2-Lyso-PAFAT Axis

“…In contrast, LysoPAFAT/LPCAT2 mRNA was undetected in T cells stimulation with or without anti-CD3 Ab for 24 h (data not shown). These results are in accord with previous reports demonstrating that LysoPAFAT activity is present in macrophages (4, 12), but not in T cells (42). The results are also consistent with our previous report that PAF plays a dominant role in the chronic phase of EAE through the activation of macrophages/microglia (16).…”

Platelet-activating factor changes in phospholipid extracts from the plasma, peripheral blood mononuclear cells and bone marrow mononuclear cells of patients with acute leukemia — A 31P MRS in vitro study

“…Moreover, membrane PAF-Rs could be detected in a histiocytic lymphoma line and in peripheral blood neutrophils and monocytes from healthy donors [20]. Additionally, the findings of Garcia et al [21] showed the ability of myeloid cell lines (HL60 and U937) to synthesize PAF, in contrast to the absence of this property in the two lymphoid cell lines (Daudi and Jurkat). The clinical studies by Gugliemi et al highlight Brought to you by | MIT Libraries Authenticated Download Date | 5/11/18 6:53 PM membrane PAF-R in several types of chronic mature B-cell malignancies: chronic lymphocytic leukemia [22], mantel B-cell lymphoma, marginal zone B-cell lymphoma, plasma cell lymhoma, prolymphocytic or prolymphocytoid B-cell leukemia, and follicular B-cell lymphoma [23].…”

Dissociation of the effects of the antitumour ether lipid ET‐18‐OCH3 on cytosolic calcium and on apoptosis

“…However, with regard to apoptosis, PAF was not able to induce DNA degradation in U937 cells and WEB‐2170 did not prevent the ET‐18‐OCH 3 ‐induced apoptosis (Figure 1a). It is interesting to note that PAF is converted to 1‐alkyl‐2‐acyl‐glycero‐3‐phosphocholine at a rate of about 50% per hour (García et al , 1991). However, even at this high rate of conversion the concentration of unmodified PAF would still be above 10 −9 m after 12 h, which is able to produce over 80% of the maximum effect on [Ca 2+ ] i (see below, Figure 4).…”