This represents an extension of our prior four year study into mechanisms of lung injury caused by generation in phagocytic cells of oxygen radicals. Based on our published (observatrions) and recent preliminary data, we plan to investigate five separate but related areas: 1. Defining the role of complement activation products not only on effector cells (neutrophils) but also on target (endothelial) cells; 2. Studying further the source and the role iron required in oxygen radical-mediated injury of endothelial cells and the lung microvasculature; 3. Exploring the biochemical events related to endothelial injury by activated neutrophils or H- 2-0-2; 4. Determining the source(s) of eicosanoids appearing during the cause of complement dependent and oxygen radical mediated lung injury; and 5. Pursuing preliminary evidence that the peptides IL-1 and tumor necrosis factor facilitate oxygen radical mediated lung injury by enhancement of oxygen radical generation from phagocytes and generation of relevant of mRNA's. For those experiments, we will use a variety of in vivo, ex vivo and in vitro techniques. We anticipate these studies will significantly extend our understanding of mediator events involved in the induction of acute lung injury caused by toxic oxygen products from phagocytic cells.
| Fattahi, Fatemeh; Russell, Mark W; Malan, Elizabeth A et al. (2018) Harmful Roles of TLR3 and TLR9 in Cardiac Dysfunction Developing during Polymicrobial Sepsis. Biomed Res Int 2018:4302726 |
| Fattahi, Fatemeh; Frydrych, Lynn M; Bian, Guowu et al. (2018) Role of complement C5a and histones in septic cardiomyopathy. Mol Immunol 102:32-41 |
| Fattahi, Fatemeh; Ward, Peter A (2017) Complement and sepsis-induced heart dysfunction. Mol Immunol 84:57-64 |
| Fattahi, Fatemeh; Kalbitz, Miriam; Malan, Elizabeth A et al. (2017) Complement-induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction. FASEB J 31:4129-4139 |
| Fattahi, Fatemeh; Grailer, Jamison J; Lu, Hope et al. (2017) Selective Biological Responses of Phagocytes and Lungs to Purified Histones. J Innate Immun 9:300-317 |
| Delano, Matthew J; Ward, Peter A (2016) The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev 274:330-353 |
| Standiford, Theodore J; Ward, Peter A (2016) Therapeutic targeting of acute lung injury and acute respiratory distress syndrome. Transl Res 167:183-91 |
| Kalbitz, Miriam; Fattahi, Fatemeh; Grailer, Jamison J et al. (2016) Complement-induced activation of the cardiac NLRP3 inflammasome in sepsis. FASEB J 30:3997-4006 |
| Haggadone, Mikel D; Grailer, Jamison J; Fattahi, Fatemeh et al. (2016) Bidirectional Crosstalk between C5a Receptors and the NLRP3 Inflammasome in Macrophages and Monocytes. Mediators Inflamm 2016:1340156 |
| Delano, Matthew J; Ward, Peter A (2016) Sepsis-induced immune dysfunction: can immune therapies reduce mortality? J Clin Invest 126:23-31 |
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