Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein.

W Palinski, S Ylä-Herttuala, ME Rosenfeld… - … : An Official Journal of …, 1990 - Am Heart Assoc
W Palinski, S Ylä-Herttuala, ME Rosenfeld, SW Butler, SA Socher, S Parthasarathy
Arteriosclerosis: An Official Journal of the American Heart …, 1990Am Heart Assoc
Increasing evidence indicates that low density lipoprotein (LDL) has to be modified to induce
foam cell formation. One such modification, oxidation of LDL, generates a number of highly
reactive short chain-length aldehydic fragments of oxidized fatty acids capable of
conjugating with lysine residues of apoprotein B. By immunizing animals with homologous
malondialdehyde-modified LDL (MDA-LDL), 4-hydroxynonenal-LDL (4-HNE-LDL), and Cu+
(+)-oxidized LDL, we developed polyvalent and monoclonal antibodies against three …
Increasing evidence indicates that low density lipoprotein (LDL) has to be modified to induce foam cell formation. One such modification, oxidation of LDL, generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoprotein B. By immunizing animals with homologous malondialdehyde-modified LDL (MDA-LDL), 4-hydroxynonenal-LDL (4-HNE-LDL), and Cu+(+)-oxidized LDL, we developed polyvalent and monoclonal antibodies against three epitopes found in oxidatively modified LDL. The present article characterizes an antiserum and monoclonal antibody (MAL-2 and MDA2, respectively) specific for MDA-lysine, and an antiserum and monoclonal antibody (HNE-6 and NA59, respectively) specific for 4-HNE-lysine. In addition, a monoclonal antibody (OLF4-3C10) was developed against an as yet undefined epitope generated during Cu++ oxidation of LDL. With these antibodies, we demonstrated that MDA-lysine and 4-HNE-lysine adducts develop on apo-lipoprotein B during copper-induced oxidation of LDL in vitro. The application of these antibodies for immunocytochemical demonstration of oxidized lipoproteins in atherosclerotic lesions of progressive severity is described in the companion article. These antibodies should prove useful in studying the role of oxidatively modified lipoproteins as well as other oxidatively modified proteins in atherogenesis.
Am Heart Assoc