Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37GM029507-11
Application #
3484657
Study Section
Special Emphasis Panel (NSS)
Project Start
1982-07-01
Project End
1997-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
11
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

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
Kalbitz, Miriam; Fattahi, Fatemeh; Herron, Todd J et al. (2016) Complement Destabilizes Cardiomyocyte Function In Vivo after Polymicrobial Sepsis and In Vitro. J Immunol 197:2353-61
Fattahi, Fatemeh; Ward, Peter A (2016) Anti-inflammatory interventions-what has worked, not worked, and what may work in the future. Transl Res 167:1-6
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

Showing the most recent 10 out of 51 publications