However, PAMPs are mostly absent in sterile kidney injury, and, in the sterile kidney inflammatory macrophage, infiltration is driven mostly by DAMPs (20, 69, 107). Macrophages are well recognized for their pathogenic role in kidney inflammation and fibrosis. Acute kidney injury caused by ischemia reperfusion or cytotoxic drugs triggers a prominent infiltrate of neutrophils and natural killer cells within hours of tissue injury (72, 78, 93, 104). found that netrin-1 induced anti-inflammatory M2 macrophage polarization in vitro through activating peroxisome proliferator-activated receptor gamma (PPARγ)-dependent pathways (104). Kidney-infiltrating macrophages exhibit increased expression of OX40L, CD80, and CD86, which are markers of disease onset and remission in LN (111). The role of macrophages in clearing any infection and supporting kidney function could prove key to future treatments of kidney disease and even infectious diseases that are associated with kidney failure, like human immunodeficiency virus (HIV) and coronavirus (COVID-19). Following the deposition of immune complex in the kidney, infiltrating inflammatory cells lead to tissue injury in lupus nephritis (LN). approved final version of manuscript. 5, No. CSF-1 produced by tubular epithelial cells in IRI mice has been shown to polarize resident macrophages toward an M2 phenotype, which partially contributed to kidney repair and regeneration after IRI (2, 90, 137). 319, No. Union Physiol. Triggers of kidney cell damage recruit circulating monocytes into interstitial compartments where they differentiate into M1 or M2 macrophages, depending on the local tissue milieu. For example, adipose tissue macrophages can convert themselves from a wound-healing phenotype to a classically activated phenotype during obesity-associated inflammation (84, 85). For example, biglycan, a small leucine-rich proteoglycan, which is released from kidney resident cells during early stages of IRI, directly activates macrophages through TLR4 and TLR2, which mediate rapid activation of NF-κB and thereby stimulate the expression of inflammatory cytokines (110). However, M2 macrophages have been shown to exist in acute kidney injury such as ischemic kidney but not in most chronic kidney diseases (14). Even though CD11c has traditionally been considered to be a dendritic cell marker, both subsets showed major characteristics and functions of macrophages. Meanwhile, macrophages are also known to resolve inflammation at a later stage and heal the … 17, 13 January 2018 | Purinergic Signalling, Vol. In vitro M2a and M2c macrophages have been demonstrated to be anti-inflammatory and to reduce kidney injury (16, 130). For example, depletion of kidney macrophages by liposomal clodronate (LC) significantly improves kidney injury and function in acute ischemia reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) models (62, 68, 75). Macrophages are found in normal kidney and in increased numbers in diseased kidney, where they act as key players in renal injury, inflammation, and fibrosis. The mechanisms by which macrophages are polarized to an anti-inflammatory phenotype in the post-ischemic kidney are not well understood. Galectin-3 produced by kidney resident macrophages drives myofibroblast accumulation/activation and promotes kidney fibrosis in UUO (49). Distinct subsets of macrophages can co-exist in kidney tissue, and particular subsets can dominate at different stages of disease, from the initiation of kidney injury to recovery (FIGURE 1). When M1 macrophages were adoptively transferred early after injury, they switched to an M2 phenotype within the kidney during the later recovery phase. drafted manuscript; D.C.H. Inflammatory macrophages secrete TNF-α, IL-1β, IL-6, IL-23, reactive oxygen species (ROS), and other pro-inflammatory mediators and further amplify intrarenal inflammation and injury in a positive feedback loop (FIGURE 2), as has been discussed in ischemia-reperfusion injury (36, 61, 75), cisplatin nephrotoxicity (18, 103), anti-GBM glomerulonephritis (5, 55), lupus nephritis (7, 97, 98), renal allograft injury (63, 89), and adriamycin nephropathy (15, 129). Investigating transcriptional and chromatin-mediated control of macrophage polarization should identify novel targets and lead to the development of future macrophage-directed therapies. Two well defined phenotypes are commonly referred to as classically activated macrophages (M1 macrophages), produced by exposure to LPS or IFN-γ, and alternatively activated macrophages (M2 macrophages), produced by Th2 cytokines such as IL-4 and IL-10 (Table 1) (43). The mechanisms underlying kidney macrophage phenotypic switch from pro-inflammatory to anti-inflammatory are not well understood. Macrophages are a type of white blood cell central to the immune system that detect and engulf harmful pathogens, like viruses, bacteria and fungi, serving as helpful scavengers to fight infections. Persistent inflammatory and fiborotic factors in chronic kidney disease promote renal fibrosis. The diverse roles of macrophages, from inflammation and injury to tissue repair and remodeling, are not fully understood. These data suggest that kidney macrophages change their phenotype in response to dynamic signals from the local kidney environment. 1, 29 January 2019 | American Journal of Physiology-Renal Physiology, Vol. S1P-dependent neutrophil gelatinase-associated lipocalin (NGAL/Lcn-2) produced by these macrophages was identified as a regenerative mediator enhancing tubular epithelial cell proliferation in the repair phase of IRI. Macrophages are large, round cells that contain a central round nucleus and have abundant clear, often vacuolated, cytoplasm. 1A). In vivo modulation of macrophages is another therapeutic approach to treat kidney disease. 469, No. However, existence of profibrotic and fibrolytic macrophages has yet to be demonstrated unequivocally in vivo CKD. 4, 1 September 2016 | Archives of Toxicology, Vol. In addition, kidney fibrosis in murine obstructive nephropathy is attenuated by depletion of monocyte lineage in CD11b-DTR mice, but not dendritic cells in CD11c-DTR mice (87, 115). showed that absence of scavenging receptors on uPAR−/− macrophages led to delayed clearance of pro-fibrotic molecules, resulting in kidney fibrosis in late-stage UUO (136). 3 It is likely that anti-inflammatory effect of phagocytosis of apoptotic cells and multiple signals in the local kidney milieu determine the macrophage phenotype within the injured kidney. Pro-inflammatory macrophages contribute to the initiation and progression of kidney disease by secretion of pro-inflammatory mediators and interaction with kidney resident cells. Monocytes infiltrate the injured kidney shortly after neutrophils, differentiate into macrophages, and contribute to early tubular injury (3). Lin found that macrophage-derived Wnt7b also plays a critical role in promoting kidney regeneration via epithelial cell-cycle progression and basement membrane repair after IRI (80). Kidney macrophages display heterogeneity, which has been defined by different surface markers. Macrophage accumulation in the injured kidney involves chemokine receptor expression on circulating monocytes (38, 39, 79). The diversity of macrophage functions has led to several classification systems. 312, No. 91, No. The origins of those found in kidney tissue, however, are not as well understood. Pro-inflammatory macrophages also produce metalloproteases (MMPs) to enable their migration through basement membranes and interstitial ECM networks (117). For example, TNF-α has a critical role in mediating the kidney injury. The most common form of the disease, autosomal dominant PKD (ADPKD) affects up to 1 in 500 and costs $2 billion/year to care for those afflicted. However, it is unknown whether macrophages mainly promote kidney cell regeneration directly through cell fusion, through transformation, or via exosomes, or indirectly by helping stem cells and progenitor proliferation and differentiation. Their data suggest that angiotensin II affects the quantity and phagocytic activity of macrophages through Agtr1. Moreover, early or late treatment with the JNK inhibitor improved kidney function and attenuated glomerular and tubulointerstitial damage in the chronic anti-GBM model (35, 86). Alkali supplementation as a therapeutic in chronic kidney disease: what mediates protection? Macrophages modulated ex vivo to display an anti-inflammatory or reparative phenotype have been successfully used as a cell-based therapy in IRI. Ramesh found that inhibition of p38 MAPK activation led to decreased production of TNF-α in macrophages and resulted in less kidney injury in cisplatin nephrotoxicity (103). 14, No. However, the core genes that regulate macrophage phenotype and function are still unclear. During this phase, the interstitial microenvironment in kidney tissue is dominated by pathogen-associated molecular patterns (PAMPs) derived from microorganisms as well as by damage-associated molecular patterns (DAMPs) released by necrotic cells (4, 107, 131). 200, No. 800 Cell 166, August 11, 2016 (NTN), macrophage depletion results in less severe renal pathology (Chalmers et al., 2015), as does inhibition of FcgR signaling on myeloid cells (Sharp et al., 2013). Macrophages are involved in the formation of the niches of stem cells and progenitor cells; without macrophage help, stem cells or progenitor cells are not able to proliferate and differentiate in injured tissues (29). Unilateral ureteral obstruction (UUO) is a well characterized model for investigating the factors that contribute to kidney fibrosis (23). Lee et al. Blockade of MMP-2/MMP-9 or MMP-9 alone significantly reduced tubular cell EMT and kidney fibrosis in UUO (119). Adoptive transfer of netrin-1-treated macrophages suppressed inflammation and protected against kidney injury in IRI mice (105). We demonstrate downregulation of mitophagy regulators, mitofusin-2 (MFN2) and Parkin, downstream of PINK1 in kidney fibrosis. Recently, Wyburn et al. Nishida and colleagues demonstrated that interstitial macrophages display an anti-fibrotic role at day 14, but not at day 5, after UUO (95). Monocytes are the largest type of white blood cell. Macrophages that produce pro-inflammatory cytokines and interact with autoreactive T cells are important mediators in the progression of LN (71). All of these data indicate that macrophages display a pro-inflammatory phenotype and contribute to cisplatin-induced acute kidney injury. As mentioned above, macrophages are the predominant infiltrating cells that accumulate in the outer medulla of the postischemic kidney. Macrophages play a special role in the onset of several diseases, including acute and chronic kidney injuries. Interestingly, IFNγ-stimulated M1 macrophages injected during the repair phase switched toward an anti-inflammatory M2 phenotype within the kidney. More recently, macrophages have been classified as classically activated macrophages (M1 macrophages), wound-healing macrophages (also known as M2a), and regulatory macrophages (also known as M2c) on the basis of their fundamental activation and function . Copyright 2020 National Primate Research Centers - All Rights Reserved. Systemic macrophage depletion using LC 1 day before UUO decreased tubular cell apoptosis and kidney fibrosis, suggesting that the initial phase of macrophage infiltration may promote subsequent kidney fibrosis (118). It is generally … In this review … It is important to define the role of tissue-resident macrophages in kidney, and differences between tissue-resident and monocyte-derived macrophages in kidney immunity, homeostasis, and repair. A positive correlation between the number of interstitial macrophages and the degree of kidney injury was identified in cisplatin nephrotoxicity, suggesting that kidney macrophages play a pathogenic role in this situation (65, 76, 103). In vitro cisplatin induced enhanced expression of TLRs and their associated signaling molecules in macrophages (121). Tissue-resident macrophages have unique tissue-specific functions in maintaining homeostasis and resolving inflammation. Macrophages (abbreviated as M φ, MΦ or MP) (Greek: large eaters, from Greek μακρός (makrós) = large, φαγεῖν (phagein) = to eat) are a type of white blood cell of the immune system that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis. Macrophages are well-known for their pathogenic role in kidney fibrosis. The same strategy can be used to define transcriptional control elements in kidney macrophages. Deletion of CSF-1 significantly reduced macrophage infiltration with a remarkable reduction of tissue injury in MRL/lpr mice (60, 91). For example, one study revealed that suppression of macrophage recruitment in osteopontin-knockout mice reduces tubulointerstitial fibrosis during the recovery process of IRI (100). However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. In a recent study, Tulane National Primate Research Center (TNPRC) scientists Xuebin Qin, PhD, professor of medicine, and Fengming Liu, PhD, assistant professor of microbiology and immunology, made a new discovery about renal (kidney) macrophages that fundamentally changes the understanding of how these cells populate. 9, No. In summary, kidney macrophage origins are diverse: the early kidney is colonized by yolk sac-derived macrophages, but the resident macrophages in the early postnatal kidney are predominantly derived from EMP- and HSC-derived monocytic precursors (Figure 2). It is noted that these studies on EMT were performed in vitro, whereas the occurrence of EMT in in vivo renal fibrosis remains subject to argument (54, 59, 74). Kidney fibrosis could be a consequence of kidney injury and inflammation, which involves macrophage infiltration. 6, 9 March 2016 | Journal of the American Society of Nephrology, Vol. The methods to target specific genes of macrophages have been made possible by LysMCre mice; for example, deletion of IL-4Ra by LysMCre reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis (22, 124). However, whether in vitro macrophages can be modulated to become fibrolytic to reduce fibrosis is unknown. Furthermore, macrophages are able to secrete exosomes to aid recovery of injured cells (30). They found that the angiotensin II type 1 receptor (Agtr1) on macrophage functions to attenuate kidney fibrosis in vivo. In contrast, M2 macrophages have anti-inflammatory functions and are involved in parasite containment, wound healing, and fibrosis (94, 114). Similarly, administration of LC selectively depleted both F4/80+ macrophages and F4/80+ dendritic cells, but not F4/80− dendritic cells, in mice with UUO, resulting in attenuated tubular apoptosis and kidney fibrosis and decreased levels of the pro-fibrotic cytokine TGF-β (68). During development in the womb, immune cells called macrophages go to the kidneys, and they remain there for life. “These findings advance our current understanding of tissue-resident macrophages and may lead to promising new directions for the development of new therapeutics for kidney diseases,” explained Qin. The role of pro-inflammatory macrophages was investigated further by using adoptive transfer in anti-GBM glomerulonephritis. However, these in vitro classifications of macrophages do not necessarily reflect their true phenotypes in vivo. During the early phase of tissue damage, the kidney interstitial microenvironment is dominated by micro-organism-derived pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), as well as pro-inflammatory cytokines, which promote full activation of the pro-inflammatory M1 macrophage. Apoptotic cells and anti-inflammatory factors in post-inflammatory tissues induced anti-inflammatory macrophages, which can mediate kidney repair and regeneration. Polycystic kidney disease (PKD) is a devastating genetic disorder that is one of the most common potentially fatal inherited diseases and is the fourth leading cause of end-stage renal disease (ESRD) in the US5,6,7. 7, 5 October 2016 | Clinical Kidney Journal, Vol. 6, Copyright © 2021 the American Physiological Society, Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM, Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool, Alikhan MA, Jones CV, Williams TM, Beckhouse AG, Fletcher AL, Kett MM, Sakkal S, Samuel CS, Ramsay RG, Deane JA, Wells CA, Little MH, Hume DA, Ricardo SD, Colony-stimulating factor-1 promotes kidney growth and repair via alteration of macrophage responses, Mononuclear phagocyte system in kidney disease and repair, Toll-like receptors and danger signaling in kidney injury, Anders HJ, Banas B, Linde Y, Weller L, Cohen CD, Kretzler M, Martin S, Vielhauer V, Schlondorff D, Grone HJ, Bacterial CpG-DNA aggravates immune complex glomerulonephritis: role of TLR9-mediated expression of chemokines and chemokine receptors, Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis, Anders HJ, Vielhauer V, Eis V, Linde Y, Kretzler M, Perez de Lema G, Strutz F, Bauer S, Rutz M, Wagner H, Grone HJ, Schlondorff D, Activation of toll-like receptor-9 induces progression of renal disease in MRL-Fas(lpr) mice, Macrophage polarization in bacterial infections, Bethunaickan R, Berthier CC, Ramanujam M, Sahu R, Zhang W, Sun Y, Bottinger EP, Ivashkiv L, Kretzler M, Davidson A, A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis, Bolisetty S, Traylor AM, Kim J, Joseph R, Ricart K, Landar A, Agarwal A, Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury, Braga TT, Correa-Costa M, Guise YF, Castoldi A, de Oliveira CD, Hyane MI, Cenedeze MA, Teixeira SA, Muscara MN, Perez KR, Cuccovia IM, Pacheco-Silva A, Goncalves GM, Camara NO, MyD88 signaling pathway is involved in renal fibrosis by favoring a TH2 immune response and activating alternative M2 macrophages, Wound macrophages as key regulators of repair: origin, phenotype, and function, Cao Q, Wang C, Zheng D, Wang Y, Lee VW, Wang YM, Zheng G, Tan TK, Yu D, Alexander SI, Harris DC, Wang Y, IL-25 induces M2 macrophages and reduces renal injury in proteinuric kidney disease, Pathogenic and protective role of macrophages in kidney disease, Cao Q, Wang Y, Wang XM, Lu J, Lee VW, Ye Q, Nguyen H, Zheng G, Zhao Y, Alexander SI, Harris DC, Renal F4/80+CD11c+ mononuclear phagocytes display phenotypic and functional characteristics of macrophages in health and in adriamycin nephropathy, Cao Q, Wang Y, Zheng D, Sun Y, Wang Y, Lee VW, Zheng G, Tan TK, Ince J, Alexander SI, Harris DC, IL-10/TGF-beta-modified macrophages induce regulatory T cells and protect against adriamycin nephrosis, Carvalho-Pinto CE, Garcia MI, Mellado M, Rodriguez-Frade JM, Martin-Caballero J, Flores J, Martinez AC, Balomenos D, Autocrine production of IFN-gamma by macrophages controls their recruitment to kidney and the development of glomerulonephritis in MRL/lpr mice, Cisplatin primes murine peritoneal macrophages for enhanced expression of nitric oxide, proinflammatory cytokines, TLRs, transcription factors and activation of MAP kinases upon co-incubation with L929 cells, Macrophages: supportive cells for tissue repair and regeneration, Sterile inflammation: sensing and reacting to damage, Cho WY, Choi HM, Lee SY, Kim MG, Kim HK, Jo SK, The role of Tregs and CD11c(+) macrophages/dendritic cells in ischemic preconditioning of the kidney, Clausen BE, Burkhardt C, Reith W, Renkawitz R, Forster I, Conditional gene targeting in macrophages and granulocytes using LysMcre mice, Cochrane AL, Kett MM, Samuel CS, Campanale NV, Anderson WP, Hume DA, Little MH, Bertram JF, Ricardo SD, Renal structural and functional repair in a mouse model of reversal of ureteral obstruction, D'Souza MJ, Oettinger CW, Shah A, Tipping PG, Huang XR, Milton GV, Macrophage depletion by albumin microencapsulated clodronate: attenuation of cytokine release in macrophage-dependent glomerulonephritis, Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD, Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury, Macrophages and immunologic inflammation of the kidney, Eardley KS, Kubal C, Zehnder D, Quinkler M, Lepenies J, Savage CO, Howie AJ, Kaur K, Cooper MS, Adu D, Cockwell P, The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease, Eardley KS, Zehnder D, Quinkler M, Lepenies J, Bates RL, Savage CO, Howie AJ, Adu D, Cockwell P, The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease, The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in, Ekstrom K, Omar O, Graneli C, Wang X, Vazirisani F, Thomsen P, Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells, Ferenbach DA, Nkejabega NC, McKay J, Choudhary AK, Vernon MA, Beesley MF, Clay S, Conway BC, Marson LP, Kluth DC, Hughes J, The induction of macrophage hemeoxygenase-1 is protective during acute kidney injury in aging mice, Ferenbach DA, Ramdas V, Spencer N, Marson L, Anegon I, Hughes J, Kluth DC, Macrophages expressing heme oxygenase-1 improve renal function in ischemia/reperfusion injury, Ferenbach DA, Sheldrake TA, Dhaliwal K, Kipari TM, Marson LP, Kluth DC, Hughes J, Macrophage/monocyte depletion by clodronate, but not diphtheria toxin, improves renal ischemia/reperfusion injury in mice, Filardy AA, Pires DR, Nunes MP, Takiya CM, Freire-de-Lima CG, Ribeiro-Gomes FL, DosReis GA, Proinflammatory clearance of apoptotic neutrophils induces an IL-12(low)IL-10(high) regulatory phenotype in macrophages, Flanc RS, Ma FY, Tesch GH, Han Y, Atkins RC, Bennett BL, Friedman GC, Fan JH, Nikolic-Paterson DJ, A pathogenic role for JNK signaling in experimental anti-GBM glomerulonephritis, Inflammatory cells in ischemic acute renal failure, Fujita E, Shimizu A, Masuda Y, Kuwahara N, Arai T, Nagasaka S, Aki K, Mii A, Natori Y, Iino Y, Katayama Y, Fukuda Y, Statin attenuates experimental anti-glomerular basement membrane glomerulonephritis together with the augmentation of alternatively activated macrophages, Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury, Furuichi K, Wada T, Iwata Y, Kitagawa K, Kobayashi K, Hashimoto H, Ishiwata Y, Asano M, Wang H, Matsushima K, Takeya M, Kuziel WA, Mukaida N, Yokoyama H, CCR2 signaling contributes to ischemia-reperfusion injury in kidney, Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils, Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K, Development of monocytes, macrophages, and dendritic cells, Monocytes and macrophages: developmental pathways and tissue homeostasis, Gueler F, Park JK, Rong S, Kirsch T, Lindschau C, Zheng W, Elger M, Fiebeler A, Fliser D, Luft FC, Haller H, Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages, Han Y, Ma FY, Tesch GH, Manthey CL, Nikolic-Paterson DJ, c-fms blockade reverses glomerular macrophage infiltration and halts development of crescentic anti-GBM glomerulonephritis in the rat, Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, Greter M, Mortha A, Boyer SW, Forsberg EC, Tanaka M, van Rooijen N, Garcia-Sastre A, Stanley ER, Ginhoux F, Frenette PS, Merad M, Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes, In vitro transformation of monocytes and dendritic cells into endothelial like cells, Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, Liu FT, Hughes J, Sethi T, Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis, Hill GS, Delahousse M, Nochy D, Remy P, Mignon F, Mery JP, Bariety J, Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages, Fc dependence of macrophage accumulation and subsequent injury in experimental glomerulonephritis, Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit.
Bbva España Apk, Amazon Prime Mr Bean, Bbva Usa Virtual Card, Dremel 4v Li-ion Variable Speed Cordless Electric Rotary Tool, How To Eat Raw Cabbage, Chocolate From The 60s, Haidong Gumdo Kata, Thorichthys Ellioti Care, Amadeus Director's Cut, Manga Sarutobi Sasuke Watch Online,
