L-selectin shedding regulates post-infarction neutrophilia without altering myocardial injury or ventricular remodelling.

Myocardial infarction (MI) triggers rapid neutrophil mobilisation from the bone marrow (BM), resulting in systemic neutrophilia that is widely associated with myocardial injury. However, whether the magnitude of this response directly influences cardiac injury and subsequent ventricular remodelling remains unclear. Ectodomain shedding of L-selectin is a hallmark of neutrophil activation, although its contribution to neutrophil mobilisation following MI has not been established. Using mice expressing a non-cleavable L-selectin mutant (L(E)), we investigated the role of L-selectin shedding in post-MI neutrophilia. Under homeostatic conditions, WT and L(E) mice exhibited comparable BM neutrophil maturation and circulating neutrophil representation. Following permanent coronary ligation, however, L(E) mice exhibited markedly attenuated neutrophilia, associated with reduced circulating CXCL2 and decreased surface CXCR2 expression on BM neutrophils. Intravenous recombinant CXCL2 increased circulating neutrophil representation in WT but not L(E) mice, suggesting that impaired mobilisation cannot be explained solely by reduced ligand availability. Despite attenuated neutrophilia, myocardial neutrophil representation was comparable between genotypes at 24 hours post-MI. Circulating cardiac troponin I concentrations and MRI-quantified infarct size also showed no detectable differences. Longitudinal cardiac MRI at days 1, 14 and 28 revealed comparable ventricular structure and function, while histological scar size was similar at day 28. These findings identify L-selectin shedding as a regulator of post-MI neutrophilia and suggest that the magnitude of this systemic response can be dissociated from acute myocardial injury and subsequent ventricular remodelling.