Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions

作者：Lynette Beattie, Amy Sawtell, Jason Mann, Teija Frame, Bianca E. Teal, Fabian de Labastida Rivera, Najmeeyah Brown, Katherine Walwyn-Brown, John W. Moore, Sandy MacDonald, Eng‐Kiat Lim, Jane E. Dalton, Christian Engwerda, Kelli P. A. MacDonald, Paul M. Kaye · 发表于：Journal of Hepatology · 年份：2016 · DOI：10.1016/j.jhep.2016.05.037 · 被引用次数：261 · 研究领域：Immune cells in cancer、Immune Response and Inflammation、Phagocytosis and Immune Regulation

BACKGROUND & AIMS: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. METHODS: We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types. RESULTS: Bone marrow derived "KCs" accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide ...