Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation

Abstract

Abstract Polymorphonuclear neutrophils (PMNs) are the most abundant circulating leukocytes, and the first cells recruited to sites of tissue inflammation. Using a fixation method to preserve native CD marker expression prior to immunophenotyping, we identified a distinct population of “primed for recruitment” PMNs in healthy mouse and human blood that has high expression of adhesion and activation markers compared with the bulk resting-state PMNs. In response to acute tissue inflammation, primed PMNs (pPMNs) were rapidly depleted from the circulation and recruited to the tissue. One hour after acute peritoneal insult, pPMNs became the dominant PMN population in bone marrow (BM) and blood, returning to baseline levels with resolution of inflammation. PMN priming was induced by the granulopoietic factors granulocyte-macrophage–colony-stimulating factor (GM-CSF) and granulocyte–colony-stimulating factor (G-CSF). High levels of pPMNs were observed in neutropenic mice and in pediatric neutropenic patients who were resistant to infection, highlighting an important role of this population in innate immune function.