- Dr. Andrew D. Luster, Principal Investigator
- Dr. Leo Ginns, Co-Investigator
- Dr. John Wain, Co-Investigator
- Dr. Benjamin Medoff, Research Associate
- Massachusetts General Hospital, Charlestown, USA
- The Role of White Blood Cell Attractans in the Development of Rejection and Organ Failure after Lung Transplantation
For patients with severe lung disease, lung transplantation offers the opportunity for a better quality of life and longer survival. However, despite improvements in surgical techniques and immunosuppressive drugs, overall median survival after lung transplantation is only 3.7 years. The major obstacle in lung transplantation is the development of severe scarring of the airways, so called bronchiolitis obliterans (BO). This scarring results from repeated injuries to the airways. Rejection, a severe inflammatory reaction mediated by the immune system against the transplanted organ, is the major source of this injury. It is dependent upon the movement of lymphocytes from the blood into the transplanted lung. The chemokines are proteins that control lymphocyte movement into organs. These proteins are expressed at high levels in transplanted lungs with rejection and BO.
Our hypothesis is that the chemokines contribute to the development of rejection and BO, and that inhibition of chemokine function increases the survival of lung transplants. In our grant, we propose to determine the expression profile of chemokines and their receptors in transplanted human lungs. In addition, we will use mouse models of lung transplantation to further delineate the precise role of a number of chemokines as well as the factors that control their expression.
We feel that our proposal will expand our understanding of the mechanisms underlying rejection and BO. The chemokines may control crucial steps in the development of these processes, and thus, may be ideal targets for therapeutic intervention. Our research is the first step towards the development of novel anti-chemokine therapies that could extend the survival of people with lung transplants.