JBC Oz Biosciences

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M000937200 on March 23, 2000

J. Biol. Chem., Vol. 275, Issue 22, 16941-16947, June 2, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/22/16941    most recent
M000937200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brazil, M. I.
Right arrow Articles by Maxfield, F. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brazil, M. I.
Right arrow Articles by Maxfield, F. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Effects of Incorporation of Immunoglobulin G and Complement Component C1q on Uptake and Degradation of Alzheimer's Disease Amyloid Fibrils by Microglia*

Melanie I. BrazilDagger , Haeyong ChungDagger §, and Frederick R. MaxfieldDagger

From the Dagger  Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021 and the § Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Microglia are macrophage-like immune system cells found in the brain. They are associated with Alzheimer's Disease plaques, which contain fibrillar beta -amyloid (fAbeta ) and other components such as complement proteins. We have shown previously that murine microglia bind and internalize fAbeta microaggregates via the type A scavenger receptor, but degradation of internalized fAbeta is significantly slower than normal degradation. In this study, we compared internalization by microglia of fAbeta microaggregates to that of anti-Abeta -antibody-coated fAbeta (IgG-fAbeta ) microaggregates and found that the uptake of the latter is increased by about 1.5-fold versus unmodified fAbeta . The endocytic trafficking of IgG-fAbeta is similar to that of fAbeta microaggregates, following an endosomal/lysosomal pathway. We also compared the internalization of fAbeta microaggregates to that of complement protein, C1q-coated fAbeta microaggregates, and found that the levels of uptake are also increased by about 1.5-fold. Rates of degradation of both types of modified fAbeta microaggregates are unchanged compared with unmodified fAbeta microaggregates. We demonstrated by blocking studies that internalization of IgG-fAbeta is mediated by Fc receptors. These data suggest that, in vivo, several different microglial receptors may play a part in internalizing fAbeta , but the involvement of other receptors may not increase the degradation of fAbeta .

* This work was supported by National Institutes of Health Grant NS34761.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Weill Medical College of Cornell University, Dept. of Biochemistry, 1300 York Ave., Rm. E215, New York, NY 10021. Tel.: 212-746-6405; Fax: 212-746-8875; E-mail: frmaxfie@mail.med.cornell.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
A. Majumdar, D. Cruz, N. Asamoah, A. Buxbaum, I. Sohar, P. Lobel, and F. R. Maxfield
Activation of Microglia Acidifies Lysosomes and Leads to Degradation of Alzheimer Amyloid Fibrils
Mol. Biol. Cell, April 1, 2007; 18(4): 1490 - 1496.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
K. Tahara, H.-D. Kim, J.-J. Jin, J. A. Maxwell, L. Li, and K.-i. Fukuchi
Role of toll-like receptor signalling in A{beta} uptake and clearance
Brain, November 1, 2006; 129(11): 3006 - 3019.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. L. Patton, W. M. Kalback, C. L. Esh, T. A. Kokjohn, G. D. Van Vickle, D. C. Luehrs, Y.-M. Kuo, J. Lopez, D. Brune, I. Ferrer, et al.
Amyloid-{beta} Peptide Remnants in AN-1792-Immunized Alzheimer's Disease Patients: A Biochemical Analysis
Am. J. Pathol., September 1, 2006; 169(3): 1048 - 1063.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Bi, M. Baudry, J. Liu, Y. Yao, L. Fu, F. Brucher, and G. Lynch
Inhibition of Geranylgeranylation Mediates the Effects of 3-Hydroxy-3-methylglutaryl (HMG)-CoA Reductase Inhibitors on Microglia
J. Biol. Chem., November 12, 2004; 279(46): 48238 - 48245.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Koenigsknecht and G. Landreth
Microglial Phagocytosis of Fibrillar {beta}-Amyloid through a {beta}1 Integrin-Dependent Mechanism
J. Neurosci., November 3, 2004; 24(44): 9838 - 9846.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. S. Gelinas, K. DaSilva, D. Fenili, P. St. George-Hyslop, and J. McLaurin
Immunotherapy for Alzheimer's disease
PNAS, October 5, 2004; 101(suppl_2): 14657 - 14662.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. I. Fonseca, J. Zhou, M. Botto, and A. J. Tenner
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
J. Neurosci., July 21, 2004; 24(29): 6457 - 6465.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. Das, V. Howard, N. Loosbrock, D. Dickson, M. P. Murphy, and T. E. Golde
Amyloid-{beta} Immunization Effectively Reduces Amyloid Deposition in FcR{gamma}-/- Knock-Out Mice
J. Neurosci., September 17, 2003; 23(24): 8532 - 8538.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
R. Furlan, E. Brambilla, F. Sanvito, L. Roccatagliata, S. Olivieri, A. Bergami, S. Pluchino, A. Uccelli, G. Comi, and G. Martino
Vaccination with amyloid-{beta} peptide induces autoimmune encephalomyelitis in C57/BL6 mice
Brain, February 1, 2003; 126(2): 285 - 291.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
A. D. N. J. de Grey
An Engineer's Approach to the Development of Real Anti-Aging Medicine
Sci. Aging Knowl. Environ., January 8, 2003; 2003(1): vp1 - vp1.
[Abstract] [Full Text]

Home page
 Infect. Immun.Home page
X. Song, S. Shapiro, D. L. Goldman, A. Casadevall, M. Scharff, and S. C. Lee
Fc{gamma} Receptor I- and III-Mediated Macrophage Inflammatory Protein 1{alpha} Induction in Primary Human and Murine Microglia
Infect. Immun., September 1, 2002; 70(9): 5177 - 5184.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. T. Jantzen, K. E. Connor, G. DiCarlo, G. L. Wenk, J. L. Wallace, A. M. Rojiani, D. Coppola, D. Morgan, and M. N. Gordon
Microglial Activation and beta -Amyloid Deposit Reduction Caused by a Nitric Oxide-Releasing Nonsteroidal Anti-Inflammatory Drug in Amyloid Precursor Protein Plus Presenilin-1 Transgenic Mice
J. Neurosci., March 15, 2002; 22(6): 2246 - 2254.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. D. Webster, M. D. Galvan, E. Ferran, W. Garzon-Rodriguez, C. G. Glabe, and A. J. Tenner
Antibody-Mediated Phagocytosis of the Amyloid {{beta}}-Peptide in Microglia Is Differentially Modulated by C1q
J. Immunol., June 15, 2001; 166(12): 7496 - 7503.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.