Iron Ions and Haeme Modulate the Binding Properties of Complement Subcomponent C1q and of Immunoglobulins

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Abstract
The complement system and circulating antibodies play a major role in the defence against infection. They act at the sites of inflammation, where the harsh microenvironment and the oxidative stress lead to the release of free iron ions and haeme. The aim of this study was to analyse the consequences of the exposure of C1q and immunoglobulins to iron ions or haeme. The changes in target recognition by C1q and in the rheumatoid factor activity of the immunoglobulins were investigated. The exposure of C1q to ferrous ions increased its binding to IgG and to IgM. In contrast, haeme inhibited C1q binding to all studied targets, especially to IgG1 and C-reactive protein. Thus, the haeme released as a result of tissue damage and oxidative stress may act as a negative feedback regulator of an inappropriate complement triggering as seen in ischaemia-reperfusion tissue injury. The results also show that iron ions and haeme were able to reveal rheumatoid factor activity of IgG. The modulation of the C1q-target binding as well as the revealing of rheumatoid factor activity of IgG by exposure to redox-active agents released at the sites of inflammation may have important consequences for the understanding of the immunopathological mechanisms of inflammatory and autoimmune diseases.