title: Specific recognition of malondialdehyde and malondialdehyde acetaldehyde adducts on oxidized LDL and apoptotic cells by complement anaphylatoxin C3a.
abstract: 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<0.001) and MDA-LDL (P<0.001) compared to nonactivated samples. The amount of C3a bound to MAA-LDL was associated with total complement activity, C3a desArg concentration, and IgG antibody levels to MAA-LDL. Proteins containing MDA adducts or MAA adducts may bind C3a in vivo and contribute to inflammatory processes involving activation of the complement system in atherosclerosis.
authors.affiliation: Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, 90014 Oulu, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Veneskoski
authors.forename: S Pauliina
authors.initials: SP
authors.lastname: Turunen
authors.forename: Outi
authors.initials: O
authors.lastname: Kummu
authors.forename: Antti
authors.initials: A
authors.lastname: Nissinen
authors.forename: Sirpa
authors.initials: S
authors.lastname: Rannikko
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Levonen
authors.forename: Sohvi
authors.initials: S
authors.lastname: Hörkkö
mesh_terms: D000079:Acetaldehyde / Q000737:chemistry; D000706:Anaphylatoxins / Q000378:metabolism; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D000706:Anaphylatoxins; D019138:Antibodies, Blocking; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine; D008315:Malondialdehyde; D015926:Complement C3a; D000079:Acetaldehyde