Macrophage Phenotype in Kidney Injury and Repair

Abstract

Background: Glomerular and interstitial macrophage infiltration is a feature for both the acute and chronic kidney diseases. Macrophages have been shown to play a diverse role in kidney injury and repair. Thus, macrophages may be a key cell type in acute and chronic kidney injury and repair. Summary and Key Messages: During renal inflammation, circulating monocytes are recruited and then become activated and polarized. By adapting to the local microenvironment, macrophages can differentiate into different phenotypes and function as a double-bladed sword in different stages of kidney disease. In general, M1 macrophages play a pathogenic role in boosting inflammatory renal injury, whereas M2 macrophages exert an anti-inflammatory and wound healing (or profibrotic) role during renal repair. In this review, we highlight the phenotypic polarization of macrophages in renal diseases and dissect their distinct functions in renal injury and repair processes, respectively. Moreover, the current understanding of regulatory mechanisms on the phenotypic switch and macrophage-related therapy are also intensively discussed.

Glycoprotein non-metastatic melanoma protein b (Gpnmb) is highly expressed in macrophages of acute injured kidney and promotes M2 macrophages polarization

“…In general, kidney M1 macrophages are activated by pro-inflammatory cytokines such as IFN-γ, LPS and tumor necrosis factor (TNF)-α, while M2 polarization is initiated by the Th2 cytokines (IL-4, IL-10, IL-13 and so on). In addition, it is also confirmed that phagocytic uptaking of apoptotic cells may switch macrophages towards an M2 phenotype [5,30]. It has been reported that the role of macrophage in AKI is subpopulation-related.…”

“…In I/R kidney, macrophages polarized into different phenotypes and exerts diverse effects [5]. We have demonstrated the Gpnmb was highly expressed in macrophages of I/R kidney.…”

“…4E and F). M1 and M2 macrophages exert proinflammatory or anti-inflammatory functions by production of specific cytokines [5]. We detected the cytokines secretion of M1 and M2 BMMφ.…”

“…Macrophages have a strong plasticity in vivo and in vitro. During kidney injury process, macrophages polarized into different phenotypes in response to the local microenvironment and exerts diverse effects [5]. M1/M2 macrophages are widely used to classify phenotype [6].…”

“…M1/M2 macrophages are widely used to classify phenotype [6]. On most occasions, pro-inflammatory M1 is also called a classic activated macrophage which can be induced by interferon (IFN)-γ and lipopolysaccharide (LPS), while alternatively activated wound healing/anti-inflammatory M2 could be generated by culturing with interleukin (IL)-4 in vitro [5]. It has been demonstrated that macrophages shift their phenotype from pro-inflammatory M1 to anti-inflammatory, pro-resolving M2 macrophages, helping kidney repair following I/R [7].…”