Hemolysis occurs in wide-spread pathological conditions, such as genetic disease, infection, pregnancy complications or during medical interventions such as cardiopulmonary bypass (CPB) with heart-lung-machines. The resulting large amounts of free hemoglobin (Hb) and heme in the circulation overwhelm endogenous scavengers such as haptoglobin (Hp), hemopexin (Hpx) and transferrin (Tf).

My presentation will focus on (1) how unbound hemoglobin, heme and iron exert vasculo-toxic and pro-inflammatory effects by activating endothelial and immune cells in mouse models and patients with hemoglobinopathies. These findings highlight a potential therapeutic benefit of iron/haem scavanging therapies in these conditions.

(2) how during intravascular hemolysis, the clearance of hemolysis products from the circulation by reticuloendothelial macrophages causes an inflammatory response that damages neighboring cell types.

(3) how iron accumulation in tumor associated macrophages by treatment with super-paramagnetic iron oxide nanoparticles can be utilized to reprogram the tumor microenvironment and reduce lung cancer relapse

Recent insights from across the biomedical research community have uncovered new inorganic chemistry that regulates or disrupts key events in developmental and reproductive biology, cancer cell proliferation, autoimmune disease, neurodegenerative disease and host pathogen interactions. Indeed, these emerging inorganic phenotypes have established the quantitative requirements and temporal fluctuations in normal and disease states including precise zinc regulation in gamete maturation and fertilization across species. To better understand the mechanisms underlying these processes at the cellular and molecular level, and to extend the concept of a ‘quantitative inorganic phenotype’ an NIGMS-supported center for Quantitative Elemental Mapping for the Life Sciences (QE-Map) was established four years ago. This team has been collaborating with teams across to the globe to accelerate the development and application of quantitative element imaging and analysis technologies. The overarching goals of QE-MAP team are to (a) develop routine methods for the accurate analysis and mapping of inorganic elements from the single cell to the tissue level; b) to overcome current limitations of Laser Ablation ICP-MS and X-ray Fluorescence Microscopy XFM technologies; c) disseminate optimal methods for robust data acquisition, calibration and standardization of quantitative data; and d) to develope workflows and software that allows co-registration of images obtained from allied mapping methods (i.e. immunohistochemistry, MALDI etc).

Using examples from several Driving Biological Projects in the QE-Map consortium, this presentation provides an overview of quantitative 2D element mapping approaches and will highlight how inherent limitations are being overcome as these technologies become more widely available. DBP teams send samples to the Quantitative Bio Element Analysis and Mapping (QBEAM), a core facility at MSU which includes two ESI bioImage266 laser ablation microscopes interfaced with Tofwerk/Thermo mass spec instruments (LA-ICP-TOF-MS). Other instruments include an Agilent triple-quad 8900 QQQ-ICP-MS for bulk analysis, a combustion analyzer, ICP-OES and Zeiss Axioscan instruments for imaging and analysis of elements from carbon through the rare earth elements. We anticipate that this cross-disciplinary team science effort will facilitate the broad application of label-free, quantitative inorganic phenotype analysis at the single cell and tissue level leading to new biological understanding of health and disease.