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

Neutrophils rapidly accumulate in the heart after myocardial infarction (MI), yet bone marrow granulopoiesis peaks later, suggesting an alternative early source. Here we show in male mice that the first wave of neutrophils recruited to the ischemic heart arises from the vascular marginated pool rather than newly generated cells in the bone marrow or spleen. Using hematopoietic stem cell ablation, flow cytometry and proteomic analyses, we find that early MI-induced neutrophilia displays hallmarks of stress-induced demargination, a process in which adherent neutrophils are rapidly released into circulation. Pharmacological or genetic inhibition of norepinephrine synthesis or β-adrenergic receptor signaling in male mice suppresses neutrophil demargination and limits cardiac infiltration. Although sustained β-adrenergic blockade does not improve long-term outcomes, transient inhibition enhances cardiac remodeling and function. These findings identify stress-induced demargination as the dominant source of early post-MI neutrophils and suggest that temporally targeted β2-adrenergic modulation may help restrain acute inflammatory injury.