and specific aims): This is a renewal application for a research program that has addressed mechanisms of oxygen-radical mediated tissue injury, the role of complement in inflammatory injury, and mechanisms of local and remote injury. The past studies have identified a dual role for products of activated neutrophils and complement in upregulating vascular adhesion molecules. They have also demonstrated the ability of complement components to stimulate endothelial cells directly. The proposed studies seek to define the role of C5a and C6 dependent products in lung inflammation using immune complex deposition models or systemic activation of complement (Aim 1). The studies will evaluate how complement activation products regulate expression of vascular ICAM-1 and P-selection (Aim 2) and airway ICAM1 (Aims 3 and 4). The effects of C5a or C5b-9 on pulmonary endothelial cells from a variety of sources will be measured, using assays of neutrophil adhesion, NO production and chemokine production (Aim 5). A thermal injury model will be used to evaluate the role of C5a and C6-dependent products in local and remote organ injury, as part of an effort to understand systemic inflammatory responses (Aim 6).

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
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; 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; 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 69 publications