BACKGROUND: Prevention of chronic kidney allograft injury (CAI) is a major goal in improving kidney allograft survival; however, the mechanisms of CAI are not clearly understood. The current study investigated whether alternatively activated M2-type macrophages are involved in the development of CAI. METHODS: A retrospective study examined kidney allograft protocol biopsies (at 1 h and at years 1, 5, and 10--a total of 41 biopsies) obtained from 13 children undergoing transplantation between 1991 and 2008 who were diagnosed with CAI: interstitial fibrosis and tubular atrophy (IF/TA) not otherwise specified (IF/TA-NOS). RESULTS: Immunostaining identified a significant increase in interstitial fibrosis with accumulation of CD68 + CD163+ M2-type macrophages. CD163+ cells were frequently localized to areas of interstitial fibrosis exhibiting collagen I deposition and accumulation of α-smooth muscle actin (SMA) + myofibroblasts. There was a significant correlation between interstitial CD163+ cells and the parameters of interstitial fibrosis (p < 0.0001), and kidney function (r =-0.82, p < 0.0001). The number of interstitial CD163+ cells at years 1 and 5 also correlated with parameters of interstitial fibrosis at years 5 and 10 respectively. Notably, urine CD163 levels correlated with interstitial CD163+ cells (r = 0.79, p < 0.01) and parameters of interstitial fibrosis (p < 0.0001). However, CD3+ T lymphocytic infiltration did not correlate with macrophage accumulation or fibrosis. In vitro, dexamethasone up-regulated expression of CD163 and cytokines (TGF-β1, FGF-2, CTGF) in human monocyte-derived macrophages, indicating a pro-fibrotic phenotype. CONCLUSIONS: Our findings identify a major population of M2-type macrophages in patients with CAI, and suggest that these M2-type macrophages might promote the development of interstitial fibrosis in IF/TA-NOS.
BACKGROUND: Prevention of chronic kidney allograft injury (CAI) is a major goal in improving kidney allograft survival; however, the mechanisms of CAI are not clearly understood. The current study investigated whether alternatively activated M2-type macrophages are involved in the development of CAI. METHODS: A retrospective study examined kidney allograft protocol biopsies (at 1 h and at years 1, 5, and 10--a total of 41 biopsies) obtained from 13 children undergoing transplantation between 1991 and 2008 who were diagnosed with CAI: interstitial fibrosis and tubular atrophy (IF/TA) not otherwise specified (IF/TA-NOS). RESULTS: Immunostaining identified a significant increase in interstitial fibrosis with accumulation of CD68 + CD163+ M2-type macrophages. CD163+ cells were frequently localized to areas of interstitial fibrosis exhibiting collagen I deposition and accumulation of α-smooth muscle actin (SMA) + myofibroblasts. There was a significant correlation between interstitial CD163+ cells and the parameters of interstitial fibrosis (p < 0.0001), and kidney function (r =-0.82, p < 0.0001). The number of interstitial CD163+ cells at years 1 and 5 also correlated with parameters of interstitial fibrosis at years 5 and 10 respectively. Notably, urine CD163 levels correlated with interstitial CD163+ cells (r = 0.79, p < 0.01) and parameters of interstitial fibrosis (p < 0.0001). However, CD3+ T lymphocytic infiltration did not correlate with macrophage accumulation or fibrosis. In vitro, dexamethasone up-regulated expression of CD163 and cytokines (TGF-β1, FGF-2, CTGF) in human monocyte-derived macrophages, indicating a pro-fibrotic phenotype. CONCLUSIONS: Our findings identify a major population of M2-type macrophages in patients with CAI, and suggest that these M2-type macrophages might promote the development of interstitial fibrosis in IF/TA-NOS.
Authors: K Solez; R A Axelsen; H Benediktsson; J F Burdick; A H Cohen; R B Colvin; B P Croker; D Droz; M S Dunnill; P F Halloran Journal: Kidney Int Date: 1993-08 Impact factor: 10.612
Authors: M K Ju; K H Huh; K T Park; S J Kim; B H Cho; C D Kim; B J So; C M Kang; S Lee; D J Joo; Y S Kim Journal: Transplant Proc Date: 2013-05 Impact factor: 1.066
Authors: Xuedong Wei; Nicole M Valenzuela; Maura Rossetti; Rebecca A Sosa; Jessica Nevarez-Mejia; Gregory A Fishbein; Arend Mulder; Jayeeta Dhar; Karen S Keslar; William M Baldwin; Robert L Fairchild; Jianquan Hou; Elaine F Reed Journal: Am J Transplant Date: 2020-05-22 Impact factor: 8.086
Authors: Benjamin J Kopecky; Christian Frye; Yuriko Terada; Keki R Balsara; Daniel Kreisel; Kory J Lavine Journal: Am J Transplant Date: 2020-01-29 Impact factor: 8.086
Authors: J Furuzawa-Carballeda; N O Uribe-Uribe; J M Arreola-Guerra; R Reyes-Acevedo; M Vilatobá; A López-Toledo; G Mondragón-Salgado; R Chávez-Fernández; F López-Verdugo; G Mondragón-Ramírez; J Alberú Journal: Clin Exp Immunol Date: 2019-04-15 Impact factor: 4.330