Interaction between lymphocytes and platelets in the synthesis of prostacyclin.

Abstract

To test the hypothesis that prostacyclin (PGI2) is formed via a biochemical interaction between platelets and lymphocytes, we measured eicosanoids by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). A distinct 6-keto-prostaglandin Fl, (6KPGF1,,) peak was noted when [14Clarachidonic acid ([14CjAA) was added to the mixed cell preparations which was increased by pretreating platelets with 1-benzylimidazole (1-BI). Lymphocytes prelabeled with [14CIAA failed to form 6KPGF1, when stimulated with phytohemagglutinin (PHA) or ionophore A23187. When the prelabeled platelets were suspended together with aspirin-treated lymphocytes and stimulated with ionophore, thrombin, or collagen, a 6KPGF1, peak was detected and enhanced by 1-BI. These results were supported by quantifying the 6KPGF1, content in the HPLCpurified fraction by RIA. Adding prostaglandin H2 (PGH2) directly to lymphocytes led to 6KPGF1,, production. Platelet aggregation and release were inhibited by lymphocytes in a doserelated manner. We conclude that lymphocytes possess PG12 synthase activity which is capable of converting platelet-derived PGH2 into PGI2. PGI2 formed is sufficient to inhibit platelet function.

Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids.

“…Because PGE2 is a relatively weak inhibitor of platelet aggregation, it probably did not account for the small residual inhibitory activity which did not degrade rapidly in media. Transcellular metabolism of arachidonate may occur between different cell types; in particular, both endothelial cells and lymphocytes have been shown to synthesize prostacyclin from platelet-derived prostaglandin endoperoxides (19,20). Thus, platelets could have donated prostaglandin endoperoxides to microfilariae towards the generation of prostacyclin.…”

Enhanced prostacyclin synthesis in endothelial cells by retrovirus-mediated transfer of prostaglandin H synthase cDNA.

“…Monolayers ofcells were washed twice with culture medium and were incubated with various stimulants for 1 h at 370C before the supernatant liquid was removed and assayed for 6KPGFI. by specific radioimmunoassay as described previously (28). .…”

Proinflammatory and Immunoregulatory Roles of Eicosanoids in T Cells

“…It has, however, been shown that lymphocytes are able to produce PGI 2 through a transcellular mechanism when co-cultured with human vascular endothelial cells (HUVECs) (Merhi-Soussi et al, 2000) and that a similar mechanism appears to be operating between platelets and lymphocytes (Wu et al, 1987), although in neither of these cases were T cells specifically implicated.…”