PMID- 25487670
OWN - NLM
STAT- MEDLINE
DCOM- 20160113
LR  - 20171010
IS  - 1432-198X (Electronic)
IS  - 0931-041X (Linking)
VI  - 30
IP  - 6
DP  - 2015 Jun
TI  - Alternatively activated macrophages in the pathogenesis of chronic kidney
      allograft injury.
PG  - 1007-17
LID - 10.1007/s00467-014-3023-0 [doi]
AB  - 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 alpha-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-beta1, 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.
FAU - Ikezumi, Yohei
AU  - Ikezumi Y
AD  - Department of Pediatrics, Niigata University Medical and Dental Hospital,
      Asahimachi-dori, 951-8510, Niiagta, Japan, ikezumi@med.niigata-u.ac.jp.
FAU - Suzuki, Toshiaki
AU  - Suzuki T
FAU - Yamada, Takeshi
AU  - Yamada T
FAU - Hasegawa, Hiroya
AU  - Hasegawa H
FAU - Kaneko, Utako
AU  - Kaneko U
FAU - Hara, Masanori
AU  - Hara M
FAU - Yanagihara, Toshio
AU  - Yanagihara T
FAU - Nikolic-Paterson, David J
AU  - Nikolic-Paterson DJ
FAU - Saitoh, Akihiko
AU  - Saitoh A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141209
PL  - Germany
TA  - Pediatr Nephrol
JT  - Pediatric nephrology (Berlin, Germany)
JID - 8708728
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (Biomarkers)
RN  - 0 (CD163 antigen)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptors, Cell Surface)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Allografts
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Atrophy
MH  - Biomarkers/metabolism
MH  - Biopsy
MH  - Cells, Cultured
MH  - Child
MH  - Dexamethasone/pharmacology
MH  - Female
MH  - Fibrosis
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/therapeutic use
MH  - Kidney/*immunology/metabolism/pathology
MH  - Kidney Transplantation/*adverse effects
MH  - *Macrophage Activation/drug effects
MH  - Macrophages/drug effects/*immunology/metabolism
MH  - Male
MH  - Phenotype
MH  - Receptors, Cell Surface/metabolism
MH  - Renal Insufficiency, Chronic/diagnosis/*immunology/metabolism
MH  - Retrospective Studies
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2014/12/10 06:00
MHDA- 2016/01/14 06:00
CRDT- 2014/12/10 06:00
PHST- 2014/08/12 00:00 [received]
PHST- 2014/11/20 00:00 [accepted]
PHST- 2014/11/05 00:00 [revised]
PHST- 2014/12/10 06:00 [entrez]
PHST- 2014/12/10 06:00 [pubmed]
PHST- 2016/01/14 06:00 [medline]
AID - 10.1007/s00467-014-3023-0 [doi]
PST - ppublish
SO  - Pediatr Nephrol. 2015 Jun;30(6):1007-17. doi: 10.1007/s00467-014-3023-0. Epub
      2014 Dec 9.