caa a22 4500 477132677 CHVBK 20180405111708.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1018387308517 doi (NATIONALLICENCE)springer-10.1023/A:1018387308517 Hypothesis: Iron chelation plays a vital role in neutrophilic inflammation [Elektronische Daten] [Andrew Ghio, Claude Piantadosi, Alvin Crumbliss] Neutrophil influx into tissues occurs in many diverse diseases and can be associated with both beneficial and injurious effects. We hypothesize that the stimulus for certain neutrophilic inflammatory responses can be reduced to a series of competing reactions for iron, with either a labile or reactive coordination site available, between host chelators and chelators not indigenous to that specific living system. The iron focuses the transport of host phagocytic cells through a metal catalyzed generation of oxidant sensitive mediators including cytokines and eicosanoids. Many of these products are chemotactic for neutrophils. We also postulate that the iron increases the activity of the phagocyte associated NADPH oxidoreductase in the neutrophil. The function of this enzyme is likely to be the generation of superoxide in the hostÕs attempt to chemically reduce and dislodge the iron from its chelate complex. After the reoxidation of Fe in an aerobic environment, Fe will be coordinated by host lactoferrin released by the neutrophil. When complexed by this glycoprotein, the metal does not readily undergo oxidation/reduction and is safely transported to the macrophages of the reticuloendothelial system where it is stored in ferritin. Finally, we propose that the neutrophil will attempt to destroy the chelator not indigenous to the host by releasing granular contents other than lactoferrin. Inability to eliminate the chelator allows this sequence to repeat itself, which can lead to tissue injury. Such persistence of a metal chelate in the host may be associated with biomineralization, fibrosis, and cancer. Chapman and Hall, 1997 free radicals nationallicence inflammation nationallicence iron nationallicence iron chelates nationallicence neutrophils nationallicence Ghio Andrew Effects Research Laboratory, EPA, National Health and Environmental, Research Triangle Park, NC, USA aut Piantadosi Claude Departments of Medicine, Duke University, Durham, NC, USA aut Crumbliss Alvin Chemistry, Duke University, Durham, NC, USA aut Biometals Kluwer Academic Publishers 10/2(1997-06-01), 135-142 0966-0844 10:2<135 1997 10 10534 https://doi.org/10.1023/A:1018387308517 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1018387308517 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ghio Andrew Effects Research Laboratory, EPA, National Health and Environmental, Research Triangle Park, NC, USA aut NATIONALLICENCE 700 1- Piantadosi Claude Departments of Medicine, Duke University, Durham, NC, USA aut NATIONALLICENCE 700 1- Crumbliss Alvin Chemistry, Duke University, Durham, NC, USA aut NATIONALLICENCE 773 0- Biometals Kluwer Academic Publishers 10/2(1997-06-01), 135-142 0966-0844 10:2<135 1997 10 10534 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer