A New Pharmacological Target to Reduce the Incidence of Acute Respiratory Distress Syndrome after Acute Lung Injury in Trauma Patients
Abstract
After severe injuries, the patients immune system is activated. The patients immune response to trauma and shock then triggers a series of complex molecular events and causes often additional injury of the lungs, even if the lung has not been directly injured. This secondary lung injury can lead to lung failure and is responsible for a large proportion of complications and deaths that occur when the initial injury has been survived. The mechanisms of how lung injury develops after severe trauma are largely unknown. Accordingly, drugs that could reduce lung injury and failure after severe injuries are not available, but are urgently needed. We have shown previously that ubiquitin, a protein that is present in normal blood, attenuates the immune response induced by severe injuries and that ubiquitin is as an activator of the chemokine receptor CXCR4. More importantly, we and others have shown that pharmacological CXCR4 activation has profound therapeutic potential in various species and animal models of sepsis, severe blunt trauma and hemorrhage, brain injury, polytrauma with lung contusion, and lung ischemia-reperfusion injury. In these models, CXCR4 activation conferred lung protection and reduced the development of lung failure. These findings suggest that the chemokine receptor CXCR4 is a new drug target that could be used to attenuate or prevent development of lung failure after severe injuries. Thus, a detailed understanding of the underlying molecular mechanisms and the development of new drugs that can activate CXCR4 better than existing proteins will be important for the development of drugs that can be used to reduce the incidence of lung failure in trauma patients. Within a 3-year period, the proposed research will demonstrate how CXCR4 activation protects the lungs after trauma in cell culture experiments and in animal (rodent) models. Furthermore, the proposed research will also provide the starting point for the development of a new class of drugs that could be used to reduce lung failure and to improve outcomes of severely injured combat casualties, civilian trauma victims, and in critical ill patients in general.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510262
Entities
People
- Matthias Majetschak
Organizations
- Loyola University Chicago
- United States Army