ELSEVIER SCIENCE IRELAND Atherosclerosis 107 (1994) 157-163 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ A THERO SC LERO SIS Human macrophage metabolism of low density lipoprotein oxidized by stimulated neutrophils and ferritin Dulcineia Saes Parra Abdalla* a, Luiz Fernando Bicudo Pereira Costa-Rosab, Hugo Pequeno Monteiroc, Ana Campaa, Rui Curib zyxwvutsrqponmlkjihgfedc “ Faculdade de Cihcias Farmaduticas, ‘lnstituto de Cihcias Biomkdicas, Universidade de Sio Paula, Sio Paulo, S.P., Brazil ‘Fundap-o Hemocentro de SGo Pa&. Sao Paulo. S.P., Bra51 (Received 5 November 1992; revision received 7 February 1994; accepted 8 February 1994) Abstract The metabolism of low density lipoprotein (LDL) oxidized with phorbol myristate acetate (PMA) stimulated neutro- phils plus ferritin (LDLox) by human monocyte-derived macrophage (HMDM) was studied. Binding of “‘I-labeled LDLox to HMDM and further uptake and degradation were higher than for native ‘251-labeled LDL. LDLox seems to be taken up by HMDM through the scavenger receptor as indicated by competition studies with unlabeled native and autoxidized LDL. An increased concentration of cellular cholesteryl esters was observed in HMDM exposed to LDLox. Oxidative modification of LDL increased its electrophoretic migration on agarose gel and also the fragmenta- tion of apolipoprotein B. Data suggest that LDLox is incorporated by human macrophages and can potentially induce foam-cell formation. Key words: Oxidized LDL; Neutrophils; Ferritin; Human macrophages; Foam cells 1. Introduction Monocyte-derived macrophages and macroph- age-derived foam cells are found in the atherosclerotic lesions of animals and humans [ 11. The transformation of macrophages into foam cells requires the intracellular accumulation of lip- * Corresponding author, Faculdade de CiBncias Far- mackticas, Universidade de Sao Paulo, C.P. 66083, CEP 05389-970, S$o Paula, S.P., Brazil. Fax: 55-I l-813-2197. ids delivered mainly by plasma low density lipo- protein (LDL) [2]. Native LDL is taken up by B/E receptors in macrophages at a relatively low rate without cholesteryl ester accumulation [2]. How- ever, macrophages can accumulate large amounts of cholesteryl esters by taking up chemically modi- fied or oxidized LDL by the scavenger receptor [3]. Oxidatively modified LDL has been isolated in vivo from atheromatous lesions [l] and interstitial inflammatory fluid [4]. LDL can be oxidatively modified in vitro by arterial endothelial cells, 0021-9150/94/%07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved. SSDI 002 1-9 150(94)05227-A