Neutrophil-oxidized low density lipoprotein: generation in and clearance from the plasma

The prevailing concept of an extremely rapid disappearance of 'modified' low density lipoprotein (LDL) from the circulation was reinvestigated. Rabbit LDL was 'modified' by homologous activated (phagocytosing) polymorphonuclear leucocytes (PMLN), radiolabelled with a non-degradable ligand (125I-TC-LDL) and injected into rabbits. The plasma half-lives of 'modified' and native LDL were T1/2 = 2.5 and 5.75 h, respectively. Furthermore, the possibility of LDL oxidation in plasma by stimulated PMNL was investigated. Hirudin-anticoagulated human plasma was incubated with unstimulated or stimulated autologous PMNL. Chemiluminometry (reactants with microperoxidase) of the lipid extract of plasma after incubation showed lipid peroxidation to be induced by phagocytosing, but not by quiescent, leucocytes. These findings show that in plasma, stimulated leucocytes can 'modify' LDL and the circulatory half-life of the latter enables its contribution to atherogenesis.