Table 1.
Summary of systematically reviewed literature.
| First Author | Year | Journal | In vitro | In vivo | Human tissues | Mφ phenotypes in vitro, ex vivo, and in vivo* | Main findings |
|---|---|---|---|---|---|---|---|
| de Water R | 1999 | Am J Kidney Dis | Wistar rats with EG/AC | Renal tissue from patients with oxalosis | M(-)/NA/NA M1: NA M2: NA |
ED1 and CD68 positive Mφ around the crystals | |
| de Water R | 2000 | Am J Kidney Dis | Wistar rats with EG/AC | M(-)/NA/NA M1: NA M2: NA |
ED1-positive Mφ expression (time course)/crystal encapsulation by multinucleated cells | ||
| de Water R | 2001 | Am J Kidney Dis |
I9.1 | M(-)/NA/NA M1: NA M2: NA |
Time course dissolution of internalized crystals by Mφ | ||
| Okada A | 2009 | J Bone Miner Res | C57BL/6N mice with GOX(IAI) | M(-)/NA/NA M1: NA M2: NA |
Transcriptome Mφ activation is related to spontaneous renal crystal elimination | ||
| Okada A | 2010 | J Bone Miner Res | C57BL/6N mice with GOX(IAI) | M(-)/NA/NA M1: NA M2: NA |
Pathway validation of relationship between renal crystal deposition and Mφ-related genes/Mφ phagocytosis of crystals | ||
| Singhto N | 2010 | J Proteome Res | U937 | M(-)/NA/NA M1: NA M2: NA |
COM crystals cause increased cellular apoptosis and survival including protein synthesis/stability, mRNA stability, and lipid metabolism | ||
| Singhto N | 2013 | J Proteome Res | Mφ from U937 | M(-)/NA/NA M1: NA M2: NA |
Interaction between HSP90 and F-actin for phagocytosis and migration of Mφ toward COM crystals | ||
| Zuo L | 2014 | J Urol | RAW264.7, M-1, 3T3/L1 | M(-)/NA/NA M1: NA M2: NA |
Co-culture of M-1, RAW264.7, and 3T3-L1 increase gene expression of OPN, MCP-1, and TNFα, that increases COM crystal adhesion on M-1 cells | ||
| Taguchi K | 2014 | J Am Soc Nephrol | Murine BMDM, M-1 | CSF-1 deficient mice with GOX(IAI) | M(-)/M(LPS)/M(IL-4) M1: CD11c, Ly6C M2: CD163, CD206 |
CSF-1-deficient mice have fewer M2-like Mφs, resulting in increased renal crystal deposition/M(IL-4) have more phagocytosis capacity than M(LPS) | |
| Taguchi K | 2015 | J Urol | Leptin deficient mice with EG+HFD | NA/NA/NA M1: Ccl5, Ccr7, CD11c, Il23a, Il6, Il10, Ly6C, Nos2, Tnf M2: Arg1, Ccl24, Ccr2, CD163, CD206, Chi3l3, Pparg |
Renal M1-like Mφs with crystal deposition are increased in leptin-deficient MetS model sunder hyperoxaluria and hyperlipidemia. | ||
| Taguchi K | 2016 | Sci Rep | Murine BMDM, M-1 | C57BL/6J mice with GOX((IAI) | Renal papillae from CaOx-/non-stone formers | M(-)/M(LPS+IFNγ)/M(IL-4+IL-13) M1: CCR2, CD11c, Il6, Il10, IL-10, Ly6C, Nos2, NOS2, Tnf, TNF M2: Arg1, CD163, CD206, Chi3l3, Il4, PPARG, Retnla |
M(IL-4+IL-13) attenuates while M(LPS+IFNγ) facilitates renal CaOx crystal formation/low M2-like Mφ, whereas M1-like Mϕ-related genes are expressed in papillary tissues of CaOx stone formers. |
| Williams J | 2016 | Urology | Blood samples from CaOx stone formers/controls | M(-)/NA/NA M1: NA M2: NA |
Monocyte mitochondrial function is decreased in CaOx stone formers | ||
| Kusmartsev S | 2016 | J Urol | Human Mφ-derived from buffy coat samples | M(-)/M(GM-CSF)/M(CSF-1) M1: NA M2: NA |
Ability to phagocytose CaOx stones is greater in M(M-CSF) than M(GM-CSF) and this is mediated through clathrin | ||
| Chiangjong W | 2016 | Sci Rep | U937, MDCK | M(-)/NA/NA M1: NA M2: NA |
Activation of monocytic cell migration by COM crystal-binding protein, enolase-1 | ||
| Taguchi K | 2017 | J Am Soc Nephrol | Renal papillae from CaOx-/non-stone formers | NA/NA/NA M1: NA M2: NA |
Activity and numbers of immune cells including Mφ and plasma cells are increased in RP papillary mucosa | ||
| Anders HJ | 2018 | Kidney Int | Nlrp3- and Asc-deficient mice with a sodium oxalate diet | NA/NA/NA M1: IL1b M2: CD206, TGFβ |
NLRP3 inhibition shifts M1-like Mφ to M2-like Mφ and suppressed of CaOx nephrocalcinosis-related renal fibrosis | ||
| Singhto N | 2018 | Front Immunol | U937, Mφ from U937, Jurkat | M(-)/NA/NA M1: NA M2: NA |
COM-treated macrophage exosomes enhance monocyte activity and migration, and macrophage phagocytic activity | ||
| Singhto N | 2018 | J Proteomics | Mφ from U937, MDCK | M(-)/NA/NA M1: NA M2: NA |
COM-treated Mφ exosomes are fragile and trigger MDCK cells to secrete more IL-8. | ||
| Dominguez-Gutierrez PR | 2018 | Front Immunol | THP-1 | Mφ and monocytes derived from buffy coat samples | M(-)/M(GM-CSF)/M(CSF-1) M1: CD68, CD86, Ifng, Il12, Tnf M2: CD163, CD206, Ifna2a, Ifnb, Il10 |
CaOx crystal-treated Mφ express M1-like phenotype; supernatants from CaOx-treated monocytes enhance M(CSF-1) crystal phagocytosis. | |
| Yu J | 2018 | Urolithiasis | M1Mφ from U937, HK-2 | M(-)/M(LPS)/M(IL-4) M1: CCL2, TNFα M2: TGFβ |
Increased oxidative stress, MCP-1, and OPN expression in COM-treated HK-2 by M(LPS). | ||
| Liu Q | 2019 | Kidney Blood Press Res | THP-1, HK-2 cells | M(-)/M(LPS+ IFNγ)/M(IL-4+IL-13) M1: IL-1β, IL-6, TNFα M2: IL-1ra, CD206, IL-10, TGFβ |
Protective role of M(IL-4+IL-13) against oxidative stress damage and apoptosis is via inhibition of NAPDH oxidase-ROS-p38 MAPK pathway. | ||
| Kusumi K | 2019 | Urolithiasis | Urine from kidney stone forming children/controls | NA/NA/NA M1: NA M2: NA |
Levels of MIP1β and IL-13 are significantly higher in patients with kidney stones than in controls. | ||
| Okada A | 2019 | Clin Exp Nephrol | Urine from CaOx stone formers/non-stone formers | NA/NA/NA M1: NA M2: NA |
IL-1a, IL-1b, IL-4, IL-10, and GM-CSF have potential as biomarkers for differentiating individuals with and without urinary stones | ||
| Okada A | 2019 | Kidney Blood Press Res | J774.1 | M(-)/NA/NA M1: NA M2: NA |
Diachronic elimination of engulfed COM crystals in in Mφ lysosomes | ||
| Xi J | 2019 | J Cell Physiol | HK-2 | C57BL/6J mice with GOX(IAI) | Peripheral blood from CaOx stone formers | M(-)/M(LPS+ IFNγ)/M(IL-4) M1: Ccr2, Il1b, Nos2 M2: Arg1, CD163, Il10 |
SIRT3 suppresses CaOx crystal formation by promoting M2-like Mφ via FOXO1 deacetylation |
| Zhu W | 2019 | Cell Death Dis | THP-1, RAW264.7, HK-2, M-1, HEK293 | Cdh16-ARKO mice with GOX(IAI)/SD rats with HLP | M(-)/NA/NA M1: Nos1, Ccr7, Il6, Irf5, Tnf M2: Arg1, Ccl22, CD163, CD206, Il10 |
AR alters Mφ recruitment and M2-like polarization to influence CaOx crystal deposition via miRNA-185-5p/CSF-1 signaling | |
| Chen Z | 2019 | Am J Physiol Renal Physiol | Murine BMDM | C57BL/6 mice with GOX(IAI) | M(-)/M(LPS)/M(IL-4) M1: CD11c, Il1b, Il6, Nfkb, Nos2, pSTAT1, Tnf M2: Arg1, CD163, CD206, Il4, Il10 |
Pioglitazone protects against CaOx crystal formation by promoting M2-like Mφ polarization through PPARγ-miR-23-Irf1/Pknox1 axis | |
| Liu H | 2020 | Theranostics | Murine BMDM, RTEC | C57BL/6J mice with GOX(IAI) | M(-)/NA/NA M1: CD11c, Il1b, Il6, Nos2, Tnf M2: Arg1, CD206, Il10 |
Enhanced M1-like Mφ polarization and renal injury via Nrf2-miR-93-TLR4/IRF1 axis leads to CaOx crystal formation | |
| Yang X | 2020 | Theranostics | Murine BMDM, RTEC | C57BL/6J mice with GOX(IAI) | M(-)/NA/NA M1: Il1b, Il6, Nos2, Tnf M2: Arg1, Chi3l3, Il10, Retnla |
Attenuation of CaOx crystal development and renal injury by M2 to M1 shift via AhR-miR-142a-IRF1/HIF-1α axis |
*The first row describes the in vitro and ex vivo characteristics of macrophages (non-polarized/M1-like/M2-like) in accordance with the nomenclature published in 2014 (Murray et al. Immunity). The 2nd and 3rd rows describe the markers used for M1- and M2-like detection in the literature, respectively.
Cell lines and animals: 3T3/L1, murine adipocytes; Cdh16-ARKO, renal tubule-specific androgen receptor knockout; HEK-293, human embryonic kidney cells; HK-2, human proximal tubule epithelial cells; I9.1, murine macrophages; J774.1, murine macrophages; Jurkat, human T lymphocytes; M-1, murine collecting duct; MDCK, canine renal tubular epithelial cells; RAW264.7, murine macrophages; SD rats, Sprague Dawley rats; THP-1, human monocytes; U937, human monocytes.
AC, ammonium chloride; AR, androgen receptor; Arg1, Arginase 1; ASC, apoptosis-associated speck-like protein; BMDM, bone marrow derived macrophages; Ccl, C-C motif chemokine ligand; Ccr, C-C chemokine receptor; Chi3l3, Chitinase 3-like 3; COM, calcium oxalate monohydrate; CSF-1, colony stimulating factor-1; EG, ethylene glycol; FOXO1, forkhead box O1; GM-CSF, granulate macrophage colony stimulating factor-1; HFD, high fat diet; HLP, hydroxy-L-proline; HSP, heat shock protein; IAI, intraabdominal injection; IFN, interferon; Irf, interferon regulatory factor; Mφ, macrophage; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemotactic protein-1; MetS, metabolic syndrome; MIP1β, macrophage inflammatory protein-1β; NA, not applicable; Nos1, Nitric oxide synthase 1; Nfkb, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3;OPN, osteopontin; PET-CT, positron emission tomography-computed tomography; PPARγ, peroxisome proliferator-activated receptor-gamma; Retnla, Resistin-like molecule alpha; ROS, reactive oxygen species; RP, Randall’s plaque; RTEC, renal tubular epithelial cell; SIRT3, sirtuin 3; TNFα, tumor necrosis factor alpha.;