Abstract

We have found that both reperfusion injury and thermal burns are critically dependent on a single natural IgM specificity, Without the IgM, injury is signficantly diminished. We have now identified potential antigens to which the IgM and used short peptide fragments to inhibit the evolution of injury in mice that respond normally to injury otherwise. This proposal seeks to determine whether humans manifest a similar pathbiology that is dependent on a limited number of natural antibody specificities. In addition, the proposal seeks to determine whether there are more severe conditions of injury in which these mechanisms no longer apply, and why.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM052585-16
Application #
8134269
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
16
Fiscal Year
2010
Total Cost
$422,821
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Sadeghipour, Hamed; Torabi, Radbeh; Gottschall, James et al. (2017) Blockade of IgM-Mediated Inflammation Alters Wound Progression in a Swine Model of Partial-Thickness Burn. J Burn Care Res 38:148-160
Sheu, Eric G; Wakatsuki, Kohei; Oakes, Sean et al. (2016) Prevention of intestinal ischemia-reperfusion injury in humanized mice. Surgery 160:436-42
Bankova, L G; Dwyer, D F; Liu, A Y et al. (2015) Maturation of mast cell progenitors to mucosal mast cells during allergic pulmonary inflammation in mice. Mucosal Immunol 8:596-606
Dwyer, Daniel F; Woodruff, Matthew C; Carroll, Michael C et al. (2014) B cells regulate CD4+ T cell responses to papain following B cell receptor-independent papain uptake. J Immunol 193:529-39
Bankova, Lora G; Lezcano, Cecilia; Pejler, Gunnar et al. (2014) Mouse mast cell proteases 4 and 5 mediate epidermal injury through disruption of tight junctions. J Immunol 192:2812-20
Houde, Martin; Jamain, Marc-David; Labonte, Julie et al. (2013) Pivotal role of mouse mast cell protease 4 in the conversion and pressor properties of Big-endothelin-1. J Pharmacol Exp Ther 346:31-7
Gurish, Michael F; Austen, K Frank (2012) Developmental origin and functional specialization of mast cell subsets. Immunity 37:25-33
Younan, George J; Heit, Yvonne I; Dastouri, Pouya et al. (2011) Mast cells are required in the proliferation and remodeling phases of microdeformational wound therapy. Plast Reconstr Surg 128:649e-58e
Afnan, Jalil; Ahmadi-Yazdi, Cyrus; Sheu, Eric G et al. (2010) Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species. Am J Physiol Regul Integr Comp Physiol 298:R1675-81
Haas, Michael S; Alicot, Elisabeth M; Schuerpf, Franziska et al. (2010) Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction. Cardiovasc Res 87:618-27

Showing the most recent 10 out of 34 publications