Abstract 15503: Myocardial Infarction Increases Diversity of Neutrophil Immunophenotype

Abstract

Background: Following myocardial infarction (MI), immune cells are recruited to clear apoptotic cells and facilitate replacement fibrosis. Neutrophils are the first immune cells recruited, and neutrophilia predicts death and adverse outcomes post-MI. Increased demand for neutrophils is met through emergency granulopoiesis. Methods and Results: Our prior investigations stimulating emergency granulopoiesis with injections of exogenous granulocyte-colony stimulating factor (G-CSF; 100 μg/kg/d) indicated neutrophil immunophenotypic diversity with the emergence of CD101 Neg neutrophils in peripheral blood and spleen. In this study, we tested our hypothesis that MI induced emergency granulopoiesis increases neutrophil phenotypic diversity. We used a non-reperfused MI model in C57BL/6J mice (females, 14-20 wk). At 1, 2, 3, and 7 d post-MI, we harvested bone marrow, peripheral blood, spleens, and hearts. Neutrophil immunophenotypes were quantified in dissociated tissues via flow cytometry. Agreeing with previous findings, neutrophil infiltration of the heart was observed at 1-3 d, reaching a climax at 2 d. Our data demonstrates novel CD101 Neg and CD117 Pos neutrophils present in the heart 1-3 d post-MI (n=3-6, p< 0.05). Additionally, elevated numbers of neutrophils and CD101 Neg neutrophil subtypes were observed in bone marrow, peripheral blood, and spleen relative to naïve mice (n=3-10, p<0.05). Conclusion: We conclude that post-MI production of neutrophils results in the recruitment of diverse neutrophil subtypes to the heart. Future studies will seek to understand how post-MI activation of emergency granulopoiesis instigates neutrophil diversity and how CD101 Neg and CD117 Pos neutrophils are involved in replacement fibrosis. Figure 1. Presence of CD101 Neg and CD117 Pos Neutrophils in the Heart in post-MI. Gating (A-C) and quantification (E-G) of neutrophil immunophenotypes. (n=6-9, Mixed Affects Two-way ANOVA with Multiple Comparisons).