Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status

Tinckam, Kathryn; Djurdjev, Ognjenka; Magil, Alex B.

doi:10.1111/j.1523-1755.2005.00606.x

Cited by 133 publications

(96 citation statements)

References 37 publications

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“…29 In our model, passive transfer of alloantibodies also increased macrophage infiltrates in the grafts. In comparison, only minor numbers of neutrophils were found.…”

Section: Macrophage Localization and Formation Of Macrophage-plateletmentioning

confidence: 78%

“…1 This was accompanied by increased macrophage infiltrates in the same range as reported for AMR in clinical studies. 28,29,31 In addition, electron micrographs showed evidence of endothelial cell injury, including swelling, blebbing, and expansion of subendothelial space, that have been associated with AMR clinically. 24 Immunohistology of five clinical biopsies diagnosed with AMR by Banff criteria 1,2,26,27 showed aggregates of CD41-positive platelets, and the distribution of the platelet aggregates correlated with the Banff injury scores.…”

Section: Discussionmentioning

confidence: 99%

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Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Kuo

Fan²,

Dvorina³

et al. 2015

Journal of the American Society of Nephrology

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Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100-to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.

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“…29 In our model, passive transfer of alloantibodies also increased macrophage infiltrates in the grafts. In comparison, only minor numbers of neutrophils were found.…”

Section: Macrophage Localization and Formation Of Macrophage-plateletmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Kuo

Fan²,

Dvorina³

et al. 2015

Journal of the American Society of Nephrology

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“…Neutrophils in capillaries are characteristically but not always found. Macrophages are now recog-nized as a common intracapillary cell in AHR in kidney (14) and heart (15) allografts. Typically, the PTC are dilated.…”

Section: Acute Humoral Rejectionmentioning

confidence: 99%

Antibody-Mediated Renal Allograft Rejection

Colvin

2007

Journal of the American Society of Nephrology

493

447

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Alloantibodies to HLA class I or II and other antigens expressed by endothelium cause a variety of effects on renal transplants, ranging from acute to chronic rejection, and even apparent graft acceptance (accommodation). Recognition of these conditions and appropriate therapy requires demonstration of C4d in biopsies, commonly confirmed by tests for circulating alloantibody. Substantial practical experience by pathologists in the interpretation and pitfalls of C4d stains are reviewed along with considerations of the clinical significance and pathologic mechanisms of the different effects of antibody on the endothelium of the renal allograft. Clinical trials will be needed to ascertain the optimal treatment for the newly appreciated conditions chronic humoral rejection and accommodation.

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“…The inflammatory cell infiltration of the allograft is a hallmark of allograft rejection (37,38). Therefore, we performed immunohistochemistry for different cell subsets to elucidate the composition of the cell infiltrates.…”

Section: Upar Deficiency Of the Allograft And Inflammatory Cell Infilmentioning

confidence: 99%

Renal Urokinase-Type Plasminogen Activator (uPA) Receptor but not uPA Deficiency Strongly Attenuates Ischemia Reperfusion Injury and Acute Kidney Allograft Rejection

Gueler

Rong

Mengel

et al. 2008

The Journal of Immunology

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Central mechanisms leading to ischemia induced allograft rejection are apoptosis and inflammation, processes highly regulated by the urokinase-type plasminogen activator (uPA) and its specific receptor (uPAR). Recently, up-regulation of uPA and uPAR has been shown to correlate with allograft rejection in human biopsies. However, the causal connection of uPA/uPAR in mediating transplant rejection and underlying molecular mechanisms remain poorly understood. In this study, we evaluated the role of uPA/uPAR in a mice model for kidney ischemia reperfusion (IR) injury and for acute kidney allograft rejection. uPAR but not uPA deficiency protected from IR injury. In the allogenic kidney transplant model, uPAR but not uPA deficiency of the allograft caused superior recipient survival and strongly attenuated loss of renal function. uPAR-deficient allografts showed reduced generation of reactive oxygen species and apoptosis. Moreover, neutrophil and monocyte/macrophage infiltration was strongly attenuated and up-regulation of the adhesion molecule ICAM-1 was completely abrogated in uPAR-deficient allografts. Inadequate ICAM-1 up-regulation in uPAR−/− primary aortic endothelial cells after C5a and TNF-α stimulation was confirmed by in vitro experiments. Our results demonstrate that the local renal uPAR plays an important role in the apoptotic and inflammatory responses mediating IR-injury and transplant rejection.

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Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status

Abstract: The results demonstrate that glomerular MO infiltration is an independent predictor of worse outcomes posttransplant following acute renal allograft rejection.

Cited by 133 publications

References 37 publications

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-Mediated Renal Allograft Rejection

Renal Urokinase-Type Plasminogen Activator (uPA) Receptor but not uPA Deficiency Strongly Attenuates Ischemia Reperfusion Injury and Acute Kidney Allograft Rejection

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