Abstract

This is a competitive renewal of an R29 award in which the Principal Investigator has found that inhibition of complement with C-1 esterase inhibitor or soluble complement receptor type I has consistently attenuated I/R injury in animals. In the R29 portion of the preliminary work, the Principal Investigator has demonstrated that specific inhibition of C5a or inhibition of C5a and C5b-9 also decrease infarct size, neutrophil infiltration and apoptosis following myocardial I/R. The PI notes that myocardial vascular endothelium appears to be the site of initial complement activation during reperfusion. The global goal of the current investigations is to delineate the role of complement in myocardial I/R injury and to characterize the molecular mechanisms of complement activation during myocardial I/R.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL052886-07
Application #
6389384
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Massicot-Fisher, Judith
Project Start
1995-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
7
Fiscal Year
2001
Total Cost
$403,468
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Li, Qian; Li, Yong Xing; Douthitt, Kelsey et al. (2012) Role of the alternative and classical complement activation pathway in complement mediated killing against Streptococcus pneumoniae colony opacity variants during acute pneumococcal otitis media in mice. Microbes Infect 14:1308-18
Pavlov, Vasile I; La Bonte, Laura R; Baldwin, William M et al. (2012) Absence of mannose-binding lectin prevents hyperglycemic cardiovascular complications. Am J Pathol 180:104-12
Burk, Anne-Maud; Martin, Myriam; Flierl, Michael A et al. (2012) Early complementopathy after multiple injuries in humans. Shock 37:348-54
Li, Qian; Li, Yong Xing; Stahl, Gregory L et al. (2011) Essential role of factor B of the alternative complement pathway in complement activation and opsonophagocytosis during acute pneumococcal otitis media in mice. Infect Immun 79:2578-85
Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru et al. (2011) Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation. Immunobiology 216:96-102
Busche, Marc N; Stahl, Gregory L (2010) Role of the complement components C5 and C3a in a mouse model of myocardial ischemia and reperfusion injury. Ger Med Sci 8:
Tong, Hua Hua; Li, Yong Xing; Stahl, Gregory L et al. (2010) Enhanced susceptibility to acute pneumococcal otitis media in mice deficient in complement C1qa, factor B, and factor B/C2. Infect Immun 78:976-83
Michelow, Ian C; Dong, Mingdong; Mungall, Bruce A et al. (2010) A novel L-ficolin/mannose-binding lectin chimeric molecule with enhanced activity against Ebola virus. J Biol Chem 285:24729-39
Busche, Marc N; Pavlov, Vasile; Takahashi, Kazue et al. (2009) Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin. Am J Physiol Heart Circ Physiol 297:H1853-9
Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C et al. (2009) Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury. Mol Immunol 47:506-10

Showing the most recent 10 out of 18 publications