Home >> Redox Report, Volume 7, Number 2

Low-density lipoprotein modification by normal, myeloperoxidase-deficient and NADPH oxidase-deficient granulocytes and the impact of redox active transition metal ions

Authors: Gerber, Claudia1; Bruchelt, Gernot2; Ledinski, Gerhard3; Greilberger, Joachim1; Niethammer, Dietrich1; Jürgens, Günther3

Source: Redox Report, Volume 7, Number 2, April 2002 , pp. 111-119(9)

Publisher: Maney Publishing

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Abstract:

The modification of low-density lipoprotein (LDL) by normal, myeloperoxidase (MPO)-deficient and NADPH oxidase-deficient granulocytes was investigated using the monoclonal antibody (mAb) OB/04, which was originally generated against copper-oxidized LDL. Incubation of LDL with normal granulocytes increased the reactivity of LDL with mAb OB/04. These effects were even more pronounced using MPO-deficient granulocytes. Inhibitors of oxidative reactions (the NADPH oxidase inhibitor diphenyleneiodonium chloride [DPI], catalase, superoxide dismutase [SOD]) did not significantly reduce LDL oxidation by normal granulocytes. Furthermore, granulocytes of a patient with NADPH oxidase deficiency were almost equally effective as normal granulocytes, indicating that oxidative burst-derived reactive oxygen species are of only minor importance in the generation of mAb OB/04-detectable new epitopes on LDL in vitro. In contrast, incubation of LDL with iron and copper prior to and during incubation with normal granulocytes markedly enhanced the generation of OB/04-detectable epitopes. It is supposed that, besides superoxide (in normal and MPO-deficient granulocytes) or instead of superoxide (in NADPH oxidase-deficient granulocytes), lytic enzymes released by activated granulocytes may enhance the availability of transition metals for oxidation of LDL. Our results support the concept that transition-metal-dependent pathways of LDL oxidation in combination with degranulation products of granulocytes are important.

Keywords:

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/135100002125000343

Affiliations: 1: Department of Hematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany 2: Department of Hematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany 3: Institute of Medical Chemistry and Pregl Laboratory, Karl-Franzens University of Graz, Graz, Austria

Publication date: 2002-04-01

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