Specific recognition of malondialdehyde and malondialdehyde acetaldehyde adducts on oxidized LDL and apoptotic cells by complement anaphylatoxin C3a

• Published in: Free radical biology & medicine 2011-08, Vol.51 (4), p.834-843
• Main Authors: Veneskoski, Marja, Turunen, S. Pauliina, Kummu, Outi, Nissinen, Antti, Rannikko, Sirpa, Levonen, Anna-Liisa, Hörkkö, Sohvi
• Format: Article
• Language: English
• Subjects: acetaldehyde; Acetaldehyde - chemistry; agarose; Anaphylatoxin C3a; Anaphylatoxins - metabolism; Animals; Antibodies, Blocking - pharmacology; apoptosis; Apoptosis - drug effects; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - immunology; Atherosclerosis - metabolism; blood serum; bovine serum albumin; Cattle; Cell Line; chemiluminescence immunoassays; Complement; Complement Activation; Complement C3a - metabolism; copper; flow cytometry; fluorescent antibody technique; Free radicals; gel electrophoresis; Humans; immunoglobulin G; Lipid peroxidation; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - immunology; Lipoproteins, LDL - metabolism; low density lipoprotein; Luminescent Measurements; macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Malondialdehyde; Malondialdehyde - chemistry; Malondialdehyde - immunology; Malondialdehyde - metabolism; Malondialdehyde acetaldehyde; monoclonal antibodies; Oxidized LDL; phosphatidylcholines; Protein Binding - drug effects; Serum Albumin, Bovine - metabolism
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2011.05.029

Oxidatively modified low-density lipoproteins (Ox-LDL) and complement anaphylatoxins C3a and C5a are colocalized in atherosclerotic lesions. Anaphylatoxin C3a also binds and breaks bacterial lipid membranes and phosphatidylcholine liposomes. The role of oxidized lipid adducts in C3a binding to Ox-LDL and apoptotic cells was investigated. Recombinant human C3a bound specifically to low-density lipoprotein and bovine serum albumin modified with malondialdehyde (MDA) and malondialdehyde acetaldehyde (MAA) in chemiluminescence immunoassays. No binding was observed to native proteins, LDL oxidized with copper ions (CuOx-LDL), or phosphocholine. C3a binding to MAA-LDL was inhibited by two monoclonal antibodies specific for MAA-LDL. On agarose gel electrophoresis, C3a comigrated with MDA-LDL and MAA-LDL, but not with native LDL or CuOx-LDL. C3a bound to apoptotic cells in flow cytometry. C3a opsonized MAA-LDL and was taken up by J774A.1 macrophages in immunofluorescence analysis. Complement-activated human serum samples (n=30) showed increased C3a binding to MAA-LDL (P