The discovery that arachidonic acid metabolism in a multicellular environment could be different from that expected from the sum of individual cell types has led to the concept of transcellular metabolism. In this process, several cells can contribute to the formation of a novel compound with potent biological action. The study of this mode of synthesis is important in the context of the current appraisal of thrombotic diseases as part of an inflammatory reaction. In this context, blood cell-vessel wall interactions present a regulated expression of adhesive molecules on either type of cell. These complex processes are initiated by signalling molecules such as cytokines that can deeply modify the phenotype of endothelial cells, which may ultimately lead to a change in the vascular tone and to atherosclerotic complications. Such reaction processes are part of the autocrine-endocrine system whereby cells can control and modify their own phenotype through the action of a local network of mediators. In this context, arachidonic acid metabolites may be an important part of unifying signal molecules that participate in these changes. The significance of transcellular biosynthesis where combined cells acquire a different metabolic potential can be viewed as an additional modification of blood cell and vessel cell phenotype in thrombotic diseases.
Prostanoids, which include the prostaglandins (PGs) and thromboxanes (TXs), interact with a specific family of G‐protein coupled receptors, of which there are known to be five distinct types, DP, EP, FP, IP and TP, each particularly sensitive to one of the five natural prostanoids, PGD2, PGE2, PGF2(, PGI2 and TXA2, respectively. Of these, it is known that the EP receptor comprises four well‐characterized subtypes: EP1, EP2, EP3 and EP4. These receptor subtypes are widely distributed throughout mammals and other species, and show particularly high levels of expression in smooth muscle and blood platelets. Despite the fact that few of these preparations express a single receptor type/subtype in isolation, a range of useful smooth muscle and platelet assays for the various prostanoid receptors are available and are presented in this unit.
The effect of dietary manipulation on eicosanoid formation in rat peritoneal macrophages was studied in relation to some of their effector functions: cellular procoagulant activity, production of reactive oxygen species (measured as chemiluminescence), and phagocytosis of antibody-coated erythrocytes. Rats were fed adequate diets for eight weeks containing mackerel oil (MO), sunflowerseed oil (SO) or hydrogenated coconut oil (HCO). The release of eicosanoids from resident macrophages stimulated by opsonized zymosan was significantly lower for the MO group as compared to the other dietary groups. Infection of the animals via intraperitoneal injection with rat cytomegalovirus resulted in a significant decrease in eicosanoid production in all groups, irrespective of dietary fat type. However, in the HCO group a partial restoration of TXB2 and HHT production could be observed at day 10 post infection. Resident macrophages obtained from the mackerel oil fed animals showed a significantly higher procoagulant activity than those from the other diet groups. Infection of the animals resulted in an increase in procoagulant activity in all groups. In contrast, no significant differences in chemiluminescence and in phagocytosis were detected between macrophages obtained from rats fed the different diet groups. It is concluded that peritoneal macrophages obtained from mackerel oil fed rats produce less eicosanoids and are more procoagulant than those from the other dietary groups, but a viral infection eradicates these differences. Therefore, a correlation between eicosanoid formation and effector functions studied could not be established.
