Chylomicron-induced prothrombin activation and platelet aggregation.
The effects on platelet aggregation of native rat chyle chylomicrons, chylomicron remnants, and chylomicrons that had been preincubated with rat or human EDTA-plasma, serum, whole blood, or pure human prothrombin were examined. The native chyle chylomicrons did not induce platelet aggregation but decreased ADP- and thrombin-induced platelet aggregation and [14C]serotonin release. Chylomicron remnants also failed to induce platelet aggregation, but they potentiated the aggregation and the [14C]serotonin release induced by ADP and thrombin. Aggregation, after a lag phase of 15 to 20 minutes, was seen when platelets were incubated with chylomicrons that had been preincubated with plasma and then isolated as the top layer after a single centrifugation at d = 1.006. This aggregation was inhibited in a dose-dependent manner by an antiserum against prothrombin that also inhibited thrombin-induced platelet aggregation. After washing by centrifugation the plasma-preincubated chylomicrons did not induce platelet aggregation, but this effect could be restored by adding a small amount of prothrombin, which did not cause aggregation when added alone or together with native chyle chylomicrons. Addition of 2% (vol/vol) plasma, however, induced aggregation when added together with either native chyle chylomicrons or washed preincubated chylomicrons, but not when added alone. Binding of 125I-labeled prothrombin to native chyle chylomicrons was demonstrated by gradient ultracentrifugation. During incubation of washed plasma-preincubated chylomicrons with 125I-prothrombin and platelets, a significant conversion of 125I-prothrombin to 125I-prethrombin and 125I-thrombin occurred, as demonstrated by autoradiography after separation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The interaction between chylomicrons and prothrombin, and possibly other coagulation proteins, thus enhances prothrombin activation in the presence of platelets.
Xu
N
N
Department of Medicine, University Hospital of Lund, Sweden.
Ohlin
A K
AK
Nilsson
A
A
D000818:Animals; D001095:Arachidonic Acids / Q000493:pharmacokinetics; D002914:Chylomicrons / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008055:Lipids / Q000145:classification; D010974:Platelet Aggregation / Q000187:drug effects*; D011485:Protein Binding; D011516:Prothrombin / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D013917:Thrombin / Q000378:metabolism
D001095:Arachidonic Acids; D002914:Chylomicrons; D007457:Iodine Radioisotopes; D008055:Lipids; D011516:Prothrombin; D013917:Thrombin