β2 adrenergic receptors orchestrate neutrophil demargination and recruitment to the ischemic heart following myocardial infarction

ABSTRACT: Acute myocardial infarction (AMI) induces a rapid and robust inflammatory response characterized by infiltration of different immune cell types to the infarcted heart. The recruitment of immune cells is a dynamic process and consists of sequential infiltration of neutrophils, proand anti-inflammatory monocytes, and lymphocytes to the injured myocardium. neutrophils are the first responders to ischemic injury and have the ability to amplify the initial inflammatory response by deploying key alarmins such as S100A8 and S100A9. These alarmins interact with Toll-Like-Receptor (TLR4) on naïve neutrophils, prime the NLRP3 inflammasome and facilitate their migration to the bone marrow (BM). The reverse-migrated neutrophils are preferentially retained within the BM sinusoids by certain adhesion receptors, a process that is essential for the activation of Gasdermin D- dependent membrane pore formation and secretion of IL-1β. Under steady-state conditions, mature neutrophils are present in major reservoirs across the body (spleen, liver, BM, lungs, and vasculature) and are recruited following changes in homeostasis. The unique feature of neutrophils in the vasculature is their distribution into two distinct groups, the marginated and the demarginated. Firmly adherent to the vasculature walls, the marginated pool of neutrophils represents ~ 51% of neutrophils in circulation and are believed to serve as early responders. The demargination process in neutrophils is attributed to loss of adhesion molecules, and rearrangement of actin cytoskeleton within the cells. Under certain stress and inflammatory conditions, adhesion of neutrophils is altered, and the marginated cells detach and mobilize into the bloodstream, expanding the percentage of demarginated cells in the blood. We reasoned that the marginated pool of neutrophils may be mobilized to meet the sudden and increased demand of the ischemic heart. Thus, deciphering the signaling pathways that stimulate the demargination of neutrophils and their recruitment to the ischemic heart may provide a viable approach to regulate neutrophil trafficking to the heart post-MI.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neutrophil

DISEASE(S): Myocardial Ischemia

SUBMITTER: Felicia Antohe  

LAB HEAD: Felicia Antohe

PROVIDER: PXD074735 | Pride | 2026-03-20

REPOSITORIES: Pride