Low-density granulocytes in the pathogenesis of inflammatory disease

Low-density granulocytes (LDGs) are a population of predominantly neutrophils that sit within the peripheral blood mononuclear cell layer following density centrifugation. Their presence in various inflammatory conditions raises the question of their role in disease pathogenesis. LDGs may be a heterogeneous population identified to contain cells with variously activated, mature, and immature phenotypes depending on the context. There is a lack of specific marker for these cells, leading to variation in how their surface phenotype is characterized. Differences in the phenotype of LDGs from healthy individuals and during pregnancy compared with those seen in the disease state suggest that distinct subsets of LDGs emerge during inflammatory disease. Subsets of LDGs may contribute to the pathogenesis of disease through their proinflammatory functions, longevity in peripheral blood, and retention within microvascular tissue, leading to damage of endothelial cells. LDGs may also enhance the adaptive immune response through their interactions with T cells. Further research to define LDG surface phenotype and the expression and functions of distinct subsets in inflammatory diseases may identify these cells as potential therapeutic targets.