HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Deletion of activating Fcgamma receptors does not confer protection in murine cryoglobulinemia-associated membranoproliferative glomerulonephritis.

Abstract
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.
AuthorsShunhua Guo, Anja S Mühlfeld, Tomasz A Wietecha, Carine J Peutz-Kootstra, Jolanta Kowalewska, Kenneth Yi, Min Spencer, Warangkana Pichaiwong, Falk Nimmerjahn, Kelly L Hudkins, Charles E Alpers
JournalThe American journal of pathology (Am J Pathol) Vol. 175 Issue 1 Pg. 107-18 (Jul 2009) ISSN: 1525-2191 [Electronic] United States
PMID19528347 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Receptors, IgG
Topics
  • Animals
  • Cryoglobulinemia (complications, immunology)
  • Female
  • Fluorescent Antibody Technique
  • Glomerulonephritis, Membranoproliferative (etiology, immunology, pathology)
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, IgG (deficiency, genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: