PMID- 23644095
OWN - NLM
STAT- MEDLINE
DCOM- 20130920
LR  - 20220410
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 112
DP  - 2013 Jul
TI  - Complement expression in retinal pigment epithelial cells is modulated by 
      activated macrophages.
PG  - 93-101
LID - S0014-4835(13)00104-8 [pii]
LID - 10.1016/j.exer.2013.04.016 [doi]
AB  - Complement activation is involved in a variety of retinal diseases. We have shown 
      previously that a number of complement components and regulators can be produced 
      locally in the eye, and that retinal pigment epithelial (RPE) cells are the major 
      source of complement expression at the retina-choroidal interface. The expression 
      of complement components by RPE cells is regulated by inflammatory cytokines. 
      Under aging or inflammatory conditions, microglia and macrophages accumulate in 
      the subretinal space, where they are in close contact with RPE cells. In this 
      study, we investigated the effect of activated macrophages on complement 
      expression by RPE cells. Mouse RPE cells were treated with the supernatants from 
      un-activated bone marrow-derived macrophages (BM-DMs), the classically activated 
      BM-DMs (M1) and different types of the alternatively activated BM-DMs (M2a by 
      IL-4, M2b by immune complex and lipopolysaccharide (LPS), M2c by IL-10). The 
      expression of inflammatory cytokines and complement genes by RPE cells were 
      determined by real-time RT-PCR. The protein expression of CFB, C3, C1INH, and C1r 
      was examined by Western blot. Our results show that un-stimulated RPE cells 
      express a variety of complement-related genes, and that the expression levels of 
      complement regulators, including C1r, factor H (CFH), DAF1, CD59, C1INH, Crry, 
      and C4BP genes are significantly higher than those of complement component genes 
      (C2, C4, CFB, C3, and C5). Macrophage supernatants increased inflammatory 
      cytokine (IL-1beta, IL-6, iNOS), chemokine (CCL2) and complement expression in RPE 
      cells. The supernatants from M0, M2a and M2c macrophages mildly up-regulated 
      (2-3.5-fold) CFB, CFH and C3 gene expression in RPE cells, whereas the 
      supernatants from M1 and M2b macrophages massively increased (10-30-fold) CFB and 
      C3 gene expression in RPE cells. The expression of other genes, including C1r, 
      C2, C4, CFH, Masp1, C1INH, and C4BP in RPE cells was also increased by the 
      supernatants of M1 and M2b macrophages; however, the increment levels were 
      significantly lower than CFB and C3 genes. M1 and M2b macrophage supernatants 
      enhanced CFB (Bb fragment) protein expression and C3 secretion by RPE cells. M1 
      macrophages may affect complement expression in RPE cells through the STAT1 
      pathway. Our results suggest that under inflammatory conditions, activated 
      macrophages could promote the alternative pathway of complement activation in the 
      retina via induction of RPE cell CFB and C3 expression.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Luo, Chang
AU  - Luo C
AD  - Centre for Vision and Vascular Science, School of Medicine, Dentistry & 
      Biomedical Sciences, Queen's University Belfast, BT12 6BA Belfast, UK.
FAU - Zhao, Jiawu
AU  - Zhao J
FAU - Madden, Angelina
AU  - Madden A
FAU - Chen, Mei
AU  - Chen M
FAU - Xu, Heping
AU  - Xu H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130501
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Complement C3)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 9007-36-7 (Complement System Proteins)
RN  - EC 3.4.21.47 (Complement Factor B)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Complement Activation/physiology
MH  - Complement C3/metabolism
MH  - Complement Factor B/metabolism
MH  - Complement Pathway, Alternative/physiology
MH  - Complement System Proteins/*genetics/metabolism
MH  - Culture Media, Conditioned/pharmacology
MH  - Cytokines/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation/*physiology
MH  - Macrophage Activation/*physiology
MH  - Macrophages/cytology/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Real-Time Polymerase Chain Reaction
MH  - Retinal Pigment Epithelium/*metabolism
MH  - STAT1 Transcription Factor/metabolism
EDAT- 2013/05/07 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/05/07 06:00
PHST- 2012/11/16 00:00 [received]
PHST- 2013/04/17 00:00 [revised]
PHST- 2013/04/19 00:00 [accepted]
PHST- 2013/05/07 06:00 [entrez]
PHST- 2013/05/07 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - S0014-4835(13)00104-8 [pii]
AID - 10.1016/j.exer.2013.04.016 [doi]
PST - ppublish
SO  - Exp Eye Res. 2013 Jul;112:93-101. doi: 10.1016/j.exer.2013.04.016. Epub 2013 May 
      1.