PMID- 19528347
OWN - NLM
STAT- MEDLINE
DCOM- 20090715
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 175
IP  - 1
DP  - 2009 Jul
TI  - Deletion of activating Fcgamma receptors does not confer protection in murine 
      cryoglobulinemia-associated membranoproliferative glomerulonephritis.
PG  - 107-18
LID - 10.2353/ajpath.2009.081159 [doi]
AB  - Many types of glomerulonephritis are initiated by the deposition of immune 
      complexes, which induce tissue injury via either engagement of Fc receptors on 
      effector cells or via complement activation. Four murine Fcgamma receptors 
      (FcgammaRs) have been identified at present. Ligand binding to FcgammaRI, III, 
      and IV induces cell activation via the immunoreceptor tyrosine-based activation 
      motif on the common gamma chain (FcRgamma). In this study, FcRgamma chain 
      knockout (FcRgamma(-/-)) mice were crossed with thymic stromal lymphopoietin 
      transgenic (TSLPtg) mice, which develop cryoglobulinemic membranoproliferative 
      glomerulonephritis (MPGN). Female mice were studied at 30 and 50 days of age, 
      when MPGN is in early and fully developed stages, respectively. Both TSLPtg and 
      TSLPtg/FcRgamma(-/-) mice developed MPGN with massive glomerular immune deposits, 
      mesangial cell proliferation, extensive mesangial matrix accumulation, and 
      macrophage influx. TSLPtg/FcRgamma(-/-) mice had more glomerular immune complex 
      deposits and higher levels of circulating cryoglobulins, IgG2a, IgG2b, and IgM, 
      compared with TSLPtg mice. TSLPtg and TSLPtg/FcRgamma(-/-) mice developed similar 
      levels of proteinuria. These results demonstrated that deletion of activating 
      FcgammaRs does not confer protection in this model of immune complex-mediated 
      MPGN. The findings contradict accepted paradigms on the role of activating 
      FcgammaRs in promoting features of glomerulonephritis as seen in other model 
      systems. We speculate engagement of FcgammaRs on cells such as 
      monocytes/macrophages may be important for the clearance of deposited immune 
      complexes and extracellular matrix proteins.
FAU - Guo, Shunhua
AU  - Guo S
AD  - Department of Pathology, University of Washington, Seattle, WA 98195, USA.
FAU - Muhlfeld, Anja S
AU  - Muhlfeld AS
FAU - Wietecha, Tomasz A
AU  - Wietecha TA
FAU - Peutz-Kootstra, Carine J
AU  - Peutz-Kootstra CJ
FAU - Kowalewska, Jolanta
AU  - Kowalewska J
FAU - Yi, Kenneth
AU  - Yi K
FAU - Spencer, Min
AU  - Spencer M
FAU - Pichaiwong, Warangkana
AU  - Pichaiwong W
FAU - Nimmerjahn, Falk
AU  - Nimmerjahn F
FAU - Hudkins, Kelly L
AU  - Hudkins KL
FAU - Alpers, Charles E
AU  - Alpers CE
LA  - eng
GR  - DK68802/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090615
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Cryoglobulinemia/*complications/immunology
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Glomerulonephritis, Membranoproliferative/etiology/*immunology/pathology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Receptors, IgG/*deficiency/genetics
PMC - PMC2708799
EDAT- 2009/06/17 09:00
MHDA- 2009/07/16 09:00
PMCR- 2010/07/01
CRDT- 2009/06/17 09:00
PHST- 2009/06/17 09:00 [entrez]
PHST- 2009/06/17 09:00 [pubmed]
PHST- 2009/07/16 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - S0002-9440(10)60528-7 [pii]
AID - 10.2353/ajpath.2009.081159 [doi]
PST - ppublish
SO  - Am J Pathol. 2009 Jul;175(1):107-18. doi: 10.2353/ajpath.2009.081159. Epub 2009 
      Jun 15.