Thursday, November 21, 2024
11/21/2024
Cardiac arrest induces a systemic inflammatory response. Several studies have demonstrated that increased sustained inflammation is associated with poor outcomes, suggesting a possible role for anti-inflammatory and immunomodulatory therapies. However, these studies have focused on mechanisms that promote inflammation without considering protective mechanisms that are also mediated by the immune cells. Our preliminary data from human patients with cardiac arrest revealed an association between the higher number of CD73-expressing lymphocytes and favorable outcomes. CD73 is a key enzyme in the generation of adenosine, a purine nucleoside that is characterized by potent anti-inflammatory properties. Our new preliminary data generated using a mouse model of cardiac arrest and resuscitation suggest that CD73- expressing lymphocytes play a role in the control of local inflammation in the heart and brain tissues. In Specific Aim 1, we will determine the functional significance of adoptive cell therapy using protective CD73- expressing lymphocytes after an ischemia and reperfusion injury in a mouse model of cardiac arrest and cardiopulmonary resuscitation. In Specific Aim 2, we will test the hypothesis that CD73-expressing lymphocytes form T cell-monocyte complexes and promote the differentiation of monocytes toward anti- inflammatory macrophages. In Specific Aim 3, we will define molecular mechanisms involved in the formation of anti-inflammatory lymphocyte-macrophages complexes. Our new data will determine the contribution of cardiac arrest-induced inflammatory response in the heart and brain tissue damage and identify CD73/adenosine/adenosine receptors axis as a potential therapeutic approach to improve outcomes after global ischemia and reperfusion injury.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
