Glomerular monocyte/macrophage influx correlates strongly with complement activation in 1-week protocol kidney allograft biopsies

Sund, Ståle; Reisæter, Anna Varberg; Scott, Holly M.; Mollnes, Tom Eirik; Hovig, Torstein

doi:10.5414/cnp62121

Cited by 28 publications

(15 citation statements)

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“…Macrophages constitute 40-60% of infiltrating cells during acute allograft rejection. In patients with acute rejection, interstitial macrophage infiltration was significantly higher than in non-rejecting patients 31 . Recently, Kim et al 18 reported that CK2α is involved in the platelet activating factor-induced NF-κ B activation and that inhibitors for each step block inflammatory cell infiltration into tissues.…”

Section: Discussionmentioning

confidence: 77%

The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

Bang

Park

2015

Free Radical Biology and Medicine

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Section: Discussionmentioning

confidence: 77%

The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

Bang

Park

2015

Free Radical Biology and Medicine

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“…Macrophages constitute 38 to 60% of infiltrating cells during acute allograft rejection and increased influx of MO has been strongly correlated to complement activation and acute rejection in a human protocol biopsy study (49). Furthermore, it has been shown that MO infiltration 3 mo after transplantation correlated inversely with graft survival (50).…”

Section: Discussionmentioning

confidence: 98%

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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“…Macrophages constitute 40 to 60% of infiltrating cells during acute allograft rejection. 37 In a human kidney transplant biopsy study, macrophage infiltration 3 mo after transplantation correlated inversely with graft survival. 38 Furthermore, macrophage depletion reduced acute rejection in a rat model of allogeneic kidney transplant rejection.…”

Section: Discussionmentioning

confidence: 99%

Complement 5a Receptor Inhibition Improves Renal Allograft Survival

Gueler¹,

Rong²,

Gwinner³

et al. 2008

Journal of the American Society of Nephrology

105

116

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Complement activation plays a key role in mediating apoptosis, inflammation, and transplant rejection. In this study, the role of the complement 5a receptor (C5aR) was examined in human renal allografts and in an allogenic mouse model of renal transplant rejection. In human kidney transplants with acute rejection, C5aR expression was increased in renal tissue and in cells infiltrating the tubulointerstitium. Similar findings were observed in mice. When recipient mice were treated once daily with a C5aR antagonist before transplantation, long-term renal allograft survival was markedly improved compared with vehicle-treatment (75 versus 0%), and apoptosis was reduced. Furthermore, treatment with a C5aR antagonist significantly attenuated monocyte/macrophage infiltration, perhaps a result of reduced levels of monocyte chemoattractant protein 1 and the intercellular adhesion molecule 1. In vitro, C5aR antagonism inhibited intercellular adhesion molecule 1 upregulation in primary mouse aortic endothelial cells and reduced adhesion of peripheral blood mononuclear cells. Furthermore, C5aR blockade markedly reduced alloreactive T cell priming. These results demonstrate that C5aR plays an important role in mediating acute kidney allograft rejection, suggesting that pharmaceutical targeting of C5aR may have potential in transplantation medicine.

show abstract

Glomerular monocyte/macrophage influx correlates strongly with complement activation in 1-week protocol kidney allograft biopsies

Cited by 28 publications

References 0 publications

The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

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

Complement 5a Receptor Inhibition Improves Renal Allograft Survival

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