Monocytes/macrophages in renal allograft rejection

Magil, Alex B.

doi:10.1016/j.trre.2009.06.005

Cited by 78 publications

(60 citation statements)

References 115 publications

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“…Cellular infiltration is a major feature of acute renal allograft rejection and macrophages, which constitute 40 to 60% of infiltrating cells during acute renal allograft rejection, which can participate in both innate and adaptive immune responses. [32][33][34] Thus, our data support the notion that C5aR signaling contributes to renal allograft rejection by modulating cellular infiltration and macrophage accumulation within the grafts. The mechanisms by which C5a-C5aR interaction induces monocyte/macrophage infiltration/accumulation within the grafts remain to be clarified.…”

Section: Discussionsupporting

confidence: 84%

Deficiency of C5aR Prolongs Renal Allograft Survival

Li¹,

Peng²,

Xing³

et al. 2010

Journal of the American Society of Nephrology

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Interaction between C5a, a product of complement activation, and its receptor (C5aR) upregulates antigen-specific T cell responses by modulating the activation of antigen-presenting cells and T cells. Whether this C5a-C5aR interaction contributes to the immune responses that promote renal allograft rejection is unknown. Here, we found that deficiency of C5aR in both graft and recipient reduced allospecific T cell responses and prolonged renal allograft survival. In addition, lack of C5aR impaired the function of donor and recipient antigen-presenting cells and inhibited the response of recipient T cells to allostimulation. Furthermore, deficiency of C5aR in both graft and recipient reduced early inflammation in the grafts, with less cellular infiltration around the vessels and fewer F4/80 positive cells in the peritubular interstitium. These data demonstrate that C5aR is critical for a full adaptive immune response and mediates renal allograft rejection. Engagement of C5aR on dendritic cells and T cells modulates their function, enhancing allospecific T cell responses that lead to allograft rejection. Targeting C5a signaling may have therapeutic potential for T cell-mediated graft rejection.

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Section: Discussionsupporting

confidence: 84%

Deficiency of C5aR Prolongs Renal Allograft Survival

Li¹,

Peng²,

Xing³

et al. 2010

Journal of the American Society of Nephrology

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“…As in patients with antibody-mediated renal acute rejection, this is predictive of a poor prognosis [8]. C4d deposition in antibody-mediated acute rejection biopsies is associated with a high number of interstitial macrophages and glomerulitis [9,10]. Acute transplant glomerulitis, defined by the presence of mononuclear cells-predominantly macrophages-in the glomeruli and endothelial cell enlargement [6] in some cases progresses to chronic glomerulopathy, characterized by capillary basement membrane multilayering, proteinuria and decline of renal function [10,11].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of morphologic and morphometric analyses in IgA nephropathy biopsies

et al. 2016

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Background: IgA nephropathy (IgAN) exhibits a variable course ranging from a benign condition to progressive renal failure with a high proportion of patients undergoing end-stage renal disease in the long term. It is unclear how to predict the risk of this progression. Mesangial C4d deposition has been found to be associated with a poor prognosis. Our aim was to search histological lesions with possible prognostic value in IgAN biopsies performed at the time of the diagnosis. Methods: Clinical and laboratory records of 44 patients undergoing renal biopsy were reviewed. IgAN was diagnosed in 32 patients and minimal change disease (MCD) in 12. C4d deposition, glomerular endothelial cell area, glomerular and interstitial macrophages were evaluated in all biopsies. Clinical and laboratory data were available in all IgAN patients at the time of diagnosis and in 21 patients at the end of follow-up (mean follow-up 48.09 ± 19.69 months). Results: All IgAN and MCD biopsies were C4d negative. The number of glomerular macrophages and the area of glomerular endothelial cells in IgAN were greater than in MCD (P < 0.001 and P < 0.0001, respectively), indicating glomerular inflammation associated with endothelial cell enlargement. Glomerular macrophages positively correlated with diffuse IgA and fibrinogen immunoreactivity (P < 0.02 and P < 0.002, respectively). Interstitial macrophages positively correlated with segmental glomerulosclerosis (P < 0.01) and tubular atrophy (P < 0.001), according to the Oxford classification. They correlated with hypertension (P < 0.03) and renal functional impairment both at the time of biopsy and at the end of follow-up. The receiver operating characteristic analysis curve and a cut-off value of ≥19.5 macrophages per high power field showed 75.0% sensitivity and 88.9% specificity in predicting worse clinical outcome. A Poisson generalized regression fit model showed that hypertension and tubular atrophy were the most significant factors in predicting a high number of interstitial macrophages. Conclusions: The number of interstitial macrophages correlated with hypertension, histological damage, functional impairment at the time of biopsy and worse outcome. A high number of interstitial macrophages in C4d negative biopsies may allow the identification of patients at increased risk of progression to renal failure.

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“…35 In renal transplant rejection, macrophages have been identified in the inflammatory infiltrates of rejection in several studies since 1975. 36,37 Finally, the acute intestinal inflammation in inflammatory bowel diseases is characterized by replacement of the CD14 Ϫ resident gut macrophage with the inflammatory CD14 ϩ MDM in several previous reports. 26 -28 The role of the CCL5-macrophage axis in priming ITx rejection is also supported by the significant correlations demonstrated by this PBL gene and intragraft CD14 ϩ MDM with allospecific CD154 ϩ TcM at the time of ITx and during rejection.…”

Section: Discussionmentioning

confidence: 90%

Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

Ashokkumar

Ningappa

Ranganathan

et al. 2011

The American Journal of Pathology

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Recurrent rejection shortens graft survival after intestinal transplantation (ITx) in children, most of whom also experience early acute cellular rejection (rejectors). To elucidate mechanisms common to early and recurrent rejection, we used a test cohort of 20 recipients to test the hypothesis that candidate peripheral blood leukocyte genes that trigger rejection episodes would be evident late after ITx during quiescent periods in genome-wide gene expression analysis and would achieve quantitative real-time PCR replication pre-ITx (another quiescent period) and in the early post-ITx period during first rejection episodes. Eight genes were significantly up-regulated among rejectors in the late post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY, SLAMF7, TGFBR3, NKG7, SYNE1, and GK5. Only

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Monocytes/macrophages in renal allograft rejection

Cited by 78 publications

References 115 publications

Deficiency of C5aR Prolongs Renal Allograft Survival

Deficiency of C5aR Prolongs Renal Allograft Survival

Prognostic value of morphologic and morphometric analyses in IgA nephropathy biopsies

Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

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