Sources of Arachidonic Acid in Platelets, Bone, Marrow and Gastrointestinal Tract

Sammanfattning: This study investigates pathways by which the eicosanoid precursor pools in the platelets, bone marrow and the gastrointestinal (GI) mucosa are acquired and regulated, and in this context some aspects on the interaction between triglyceride (TG)-rich lipoproteins and platelets. 1. Platelets take up chylomicrons (CM) in vitro, the main part being sequestered in open canalicular system and not degraded, but do not exhibit any receptor mediated uptake and degradation of chylomicron remnants (CMR). Although CM, CMR and Intralipid affect agonist-induced platelet aggregation in vitro, CMs and CMRs are not an arachidonic acid (AA) source for platelets. The binding of prothrombin and protein S to postprandial TG-rich lipoproteins increased more after a meal rich in saturated fat than after a linoleate (LA) rich meal, which might increase platelet induced activation of these factors. 2. In rats plasma 2-arachidonyl-lysophosphatidylcholine (2-AA-LPC) supplies AA to several extrahepatic tissues, the quantitative importance being large in case of the small intestine. In guinea pigs, local desaturation-elongation of LA taken up as plasma free fatty acids (LA-FFA) is a major AA source. Bone marrow cells including megakaryocytes and the mucosa of GI tract produce much more AA than is exported from the liver. Therefore, we suggest that uptake and local interconversion of plasma LA-FFA and uptake of plasma 2-AA-LPC are two important alternative pathways for the supply of AA to extrahepatic tissues. Since platelets do not convert LA to d6-desaturase products, it is suggested that the build up of AA pools may be an integral part of the platelet formation in the bone marrow. 3. Fasting increases the rate of uptake and interconversion of plasma LA-FFA in both liver and extrahepatic tissues. The increase of plasma FFA concentration enhances the tissue uptake and this is linked to an increased rate of local interconversion of plasma LA-FFA. The concentration and composition of the plasma FFA pool as well as the regulation of desaturases activity in extrahepatic tissues during fasting is important determinants of eicosanoid precursor formation. 4. Our results challenge the common view that the liver is the main site of formation of AA which is then transported to other tissues mainly by lipoproteins. Our animal model can be used to study the rates of fatty acid desaturation and acylation in relation to enzyme activities and substrate availability in vivo.