Apoptotic PMNs are removed by macrophage- or dendritic cell-mediated phagocytosis. In the absence of infection or inflammation, PMN clearance occurs at significant rates in the spleen, liver, and bone marrow [
31]. In response to infection or inflammation, PMNs can infiltrate in and be cleared from all tissues of the body [
21]. PMN apoptosis as well as subsequent removal is a hallmark of inflammation resolution, an active process that requires activation of many inhibitory pathway cascades [
20]. For example, apoptotic PMNs produce “find me” (e.g., lipid mediators and nucleotides) and “eat me” (e.g., lysophosphatidylcholine) signals to attract scavengers by at least two different mechanisms [
20,
21]. First, apoptotic PMNs generate annexin A1 and lactoferrin to inhibit PMN infiltration. Moreover, these two mediators attract phagocytic macrophages to remove PMNs. Second, phagocytosis of apoptotic PMNs by macrophages activates an antiinflammatory pathway to inhibit proinflammatory mediators (e.g., TNF-α) and induce the production of IL-10, transforming growth factor-β and pro-resolving lipid mediators such as lipoxins, protectins, and resolvins [
32]. These pro-resolving mediators inhibit PMN transendothelial migration and scavenge chemokines and cytokines. Esmann and colleagues have recently shown that after exposure to activating stimuli (e.g., lipopolysaccharide and interferon-γ), PMNs, as a self-regulation mechanism, can ingest apoptotic PMNs and contribute to the resolution of acute inflammation [
33]. If not removed in a timely manner, dying PMNs can liberate granule components to the extracellular environment and prolong the ongoing inflammatory response [
21]. The importance of these mechanisms in the MI setting, however, needs to be investigated.