- Dr Benjamin Medoff, Principal Investigator
- Dr Andrew Luster, Research Associate
- Dr Umar Mahmood, Research Associate
- Massachusetts General Hospital, Boston, USA
- The Role of the White Blood Cell Attractant CXCL10 in the Development of Lung Injury Following Lung Transplantation
Lung transplantation is the only effective treatment for patients with severe lung disease, one of the most common causes of death in the world. Unfortunately outcomes after lung transplantation remain relatively poor, compared to other organ transplants. One of the most important causes of death after transplantation is failure of the lung to work after it is initially placed in the recipient. This failure, called primary graft dysfunction or PGD, results from injury to the lung due to the interruption of blood flow during the transplant procedure. Research has suggested that PGD results from the movement of a specific type of white blood cell, called a T lymphocyte, into the transplanted lung after it is reimplanted into the recipient. Chemokines are proteins that control the movement of white blood cells into organs.
We present data showing that a specific chemokine, CXCL10, which is known to control the movement of T lymphocytes, is produced in the lung after transplantation and in the lungs of mice in a model that simulates PGD. We hypothesize that CXCL10 is the primary controller of T lymphocyte movement into the lung immediately after transplantation and thus is a major controller of lung dysfunction after a transplant.
In this proposal we plan to determine the exact role of CXCL10 in the development of PGD. We will do this by altering the expression of CXCL10 in a mouse model of lung injury. We will also confirm our results by studying samples taken from lung transplants in humans. This study has the potential to identify a novel therapeutic target that could prevent an important complication following lung transplantation.