Macrophage diversity in renal injury and repair
Sharon D. Ricardo, … , Harry van Goor, Allison A. Eddy
Sharon D. Ricardo, … , Harry van Goor, Allison A. Eddy
Published November 3, 2008
Citation Information: J Clin Invest. 2008;118(11):3522-3530. https://doi.org/10.1172/JCI36150.
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Science in Medicine

Macrophage diversity in renal injury and repair

Abstract

Monocyte-derived macrophages can determine the outcome of the immune response and whether this response contributes to tissue repair or mediates tissue destruction. In addition to their important role in immune-mediated renal disease and host defense, macrophages play a fundamental role in tissue remodeling during embryonic development, acquired kidney disease, and renal allograft responses. This review summarizes macrophage phenotype and function in the orchestration of kidney repair and replacement of specialized renal cells following injury. Recent advances in our understanding of macrophage heterogeneity in response to their microenvironment raise new and exciting therapeutic possibilities to attenuate or conceivably reverse progressive renal disease in the context of fibrosis. Furthermore, parallels with pathological processes in many other organs also exist.

Authors

Sharon D. Ricardo, Harry van Goor, Allison A. Eddy

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Figure 1

The relationships between infiltrating macrophages and macrophage-derived products in chronic ongoing inflammation lead to structural and functional renal damage.

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The relationships between infiltrating macrophages and macrophage-derive...
In response to tubular and glomerular injury/dysfunction, macrophage chemoattractants and proteinuria promote the infiltration of renal macrophages, leading to the generation of proinflammatory cytokines, vasoactive eicosanoids, and ROS. The initial injury and proinflammatory state may lead to podocyte and tubular cell apoptosis. Overproduction of TGF-β by macrophages, myofibroblasts, and mesangial cells promotes increased synthesis of glomerular and interstitial ECM proteins and decreased matrix turnover due to the synthesis of matrix-degrading protease inhibitors. The net effect of interstitial fibrosis and/or glomerulosclerosis and podocyte and tubular cell loss is the disruption to tissue architecture and loss of renal function.