Iron is an essential growth factor for mammalian cells and microbes. Therefore bacteria have developed a system, called bacterial siderophores, to bind iron and use it for their growth and proliferation. One of the most described and important classes of siderophores are catechol siderophores. Based on previous observations, showing increased bacterial growth in the presence of catechols, we asked whether this may be referred to hormone mediated alterations of iron homeostasis.
We study the effects of catecholamines on the regulation of iron in wild-type and lipocalin-2 knockout bone marrow derived macrophages (BMDM). Lipocalin-2 is a mammalian siderophore binding peptide in order to inhibit an interaction of bacterial siderophores with iron, which would result in an increased bacterial growth. For infection assays we use the Gram negative bacteria Salmonella typhimurium (S.tm.). Administration of catechols to macrophages resulted in a dose dependent increase of heme oxygenase-1 and ferroportin expression, the latter being the major cellular iron exporter. The upregulation of the ferroportin expression could be a consequence of an increased intramacrophage iron concentration. This effect could also be reproduced upon infection of macrophages with S.tm.. These effects were independent from the presence/ absence of the siderophore binding peptide lipocalin-2. S.tm. infected macrophages, which were stimulated with catecholamines, showed an increased delivery of iron to bacteria along with an impaired pro-inflammatory immune response of macrophages.
Our data demonstrate that catecholamines may deteriorate the course of infection by promoting bacterial growth which can be a major concern for the treatment of patients with bacterial sepsis receiving catecholamines.