Depletion of Cells of Monocyte Lineage Prevents Loss of Renal Microvasculature in Murine Kidney Transplantation

Qi, Feng; Adair, Anya; Ferenbach, David A.; Vass, David G.; Mylonas, Katie J.; Kipari, Tiina; Clay, Michael; Kluth, David; Hughes, Jeremy; Marson, Lorna

doi:10.1097/tp.0b013e318188d433

Cited by 63 publications

(62 citation statements)

References 36 publications

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“…In contrast, DT administration to CD11b-DTR mice depleted F4/80 + macrophages but did not affect DCs in the spleen and lymph nodes (28). Qi et al noted similar findings using a murine kidney transplantation model that DT treatment in CD11b-DTR mice significantly reduced circulating monocytes, eliminated renal F4/80 + cells, and CD11c + cells, but had no effects on CD11c + DCs in the spleen (29). Thus, susceptibility of CD11c DCs to DT is different among the various organs in CD11b-DTR mice.…”

Section: Discussionsupporting

confidence: 56%

Renal Fibrosis in Murine Obstructive Nephropathy Is Attenuated by Depletion of Monocyte Lineage, Not Dendritic Cells

et al. 2010

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Abstract. The role of renal dendritic cells (DCs) in renal fibrosis is unknown. The present study was conducted to examine the relative role of renal DCs and macrophages in the development of renal fibrosis in murine obstructive nephropathy. CD11c-diphtheria toxin receptor (DTR) transgenic mice and CD11b-DTR transgenic mice were subjected to unilateral ureteral obstruction. To conditionally and selectively deplete DCs or macrophages, DT was given to these mice and kidneys were harvested on day 5. Ureteral obstruction elicited renal fibrosis characterized by tubulointerstitial collagen III deposition and accumulation of α-smooth muscle actin-positive cells. Flow cytometric analysis revealed a marked increase in cell counts of F4/80 + macrophages, F4/80 + DCs, as well as neutrophils and T cells in the obstructed kidney. DT administration to CD11c-DTR mice led to selective depletion of renal CD11c + DCs, but did not affect renal fibrosis. In contrast, administration of DT to CD11b-DTR mice resulted in ablation of all monocyte lineages including macrophages and DCs and attenuated renal fibrosis. Our results do not support the role of renal DCs, but confirm the importance of monocyte lineage cells other than DCs in the development of the early phase of renal fibrosis following ureteral obstruction in mice.

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Section: Discussionsupporting

confidence: 56%

Renal Fibrosis in Murine Obstructive Nephropathy Is Attenuated by Depletion of Monocyte Lineage, Not Dendritic Cells

et al. 2010

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“…In addition, blockade of macrophage colony-stimulating factor-reduced macrophage proliferation and accumulation in the graft leading to a decrease in the severity of kidney transplant rejection in mice (Jose et al 2003). Other studies have confirmed in macrophages a decreased infiltration and an increase in graft survival in murine models of both kidney (Qi et al 2008) and heart (Takeiri et al 2011) transplantation. Furthermore, in the context of human kidney transplantation, CX3CR1 expression by macrophages was associated with acute rejection, and was a negative prognostic factor in human kidney graft (Hoffmann et al 2010).…”

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confidence: 68%

Effector Mechanisms of Rejection

Moreau

Varey

Anegón

et al. 2013

Cold Spring Harbor Perspectives in Medicine

144

136

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“…Cellular immunity includes T-cell-mediated cytotoxicity and also natural killer cell-mediated and macrophagemediated cytotoxicity [17][18][19]. Humoral immunity attacks allografts by producing specific antibodies against the grafts [20][21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS

et al. 2010

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Proteomics is one of the emerging techniques for biomarker discovery. Biomarkers can be used for early noninvasive diagnosis and prognosis of diseases and treatment efficacy evaluation. In the present study, the well-established research systems of ClinProt Micro solution incorporated unique magnetic bead sample preparation technology, which, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), have become very successful in bioinformatics due to its outstanding performance and reproducibility for discovery disease-related biomarker. We collected fasting blood samples from patients with biopsy-confirmed acute renal allograft rejection (n = 12), chronic rejection (n = 12), stable graft function (n = 12) and also from healthy volunteers (n = 13) to study serum peptidome patterns. Specimens were purified with magnetic bead-based weak cation exchange chromatography and analyzed with a MALDI-TOF mass spectrometer. The results indicated that 18 differential peptide peaks were selected as potential biomarkers of acute renal allograft rejection, and 6 differential peptide peaks were selected as potential biomarkers of chronic rejection. A Quick Classifier Algorithm was used to set up the classification models for acute and chronic renal allograft rejection. The algorithm models recognize 82.64% of acute rejection and 98.96% of chronic rejection episodes, respectively. We were able to identify serum protein fingerprints in small sample sizes of recipients with renal allograft rejection and establish the models for diagnosis of renal allograft rejection. This preliminary study demonstrated that proteomics is an emerging tool for early diagnosis of renal allograft rejection and helps us to better understand the pathogenesis of disease process.

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Depletion of Cells of Monocyte Lineage Prevents Loss of Renal Microvasculature in Murine Kidney Transplantation

Abstract: These data indicate a significant role for macrophages in causing acute rejection-related tissue injury that is, at least in part, targeted to the microcirculation.

Cited by 63 publications

References 36 publications

Renal Fibrosis in Murine Obstructive Nephropathy Is Attenuated by Depletion of Monocyte Lineage, Not Dendritic Cells

Renal Fibrosis in Murine Obstructive Nephropathy Is Attenuated by Depletion of Monocyte Lineage, Not Dendritic Cells

Effector Mechanisms of Rejection

Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS

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