| Co-opting endogenous immunoglobulin for the regulation of inflammation and osteoclastogenesis in humans and mice. | |
| | |
MedLine Citation:
|
PMID: 22127707 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
OBJECTIVE: Cells of the monocytic lineage play fundamental roles in the regulation of health, ranging from the initiation and resolution of inflammation to bone homeostasis. In rheumatoid arthritis (RA), the inflamed synovium exhibits characteristic infiltration of macrophages along with local osteoclast maturation, which, together, drive chronic inflammation and downstream articular destruction. The aim of this study was to explore an entirely novel route of immunoglobulin-mediated regulation, involving simultaneous suppression of the inflammatory and erosive processes in the synovium. METHODS: Using in vivo and in vitro studies of human cells and a murine model of RA, the ability of staphylococcal protein A (SPA) to interact with and modulate cells of the monocytic lineage was tested. In addition, the efficacy of SPA as a therapeutic agent was evaluated in murine collagen-induced arthritis (CIA). RESULTS: SPA showed a capacity to appropriate circulating IgG, by generating small immunoglobulin complexes that interacted with monocytes, macrophages, and preosteoclasts. Formation of these complexes resulted in Fcγ receptor type I-dependent polarization of macrophages to a regulatory phenotype, rendering them unresponsive to activators such as interferon-γ. The antiinflammatory complexes also had the capacity to directly inhibit differentiation of preosteoclasts into osteoclasts in humans. Moreover, administration of SPA in the early stages of disease substantially alleviated the clinical and histologic erosive features of CIA in mice. CONCLUSION: These findings demonstrate the overarching utility of immunoglobulin complexes for the prevention and treatment of inflammatory diseases. The results shed light on the interface between immunoglobulin complex-mediated pathways, osteoclastogenesis, and associated pathologic processes. Thus, therapeutic agents designed to harness all of these properties may be an effective treatment for arthritis, by targeting both the innate inflammatory response and prodestructive pathways. |
| | |
Authors:
|
Lindsay M Maclellan; Jennifer Montgomery; Fujimi Sugiyama; Susan M Kitson; Katja Thümmler; Gregg J Silverman; Stephen A Beers; Robert J B Nibbs; Iain B McInnes; Carl S Goodyear |
Related Documents
:
|
15751777 - Tubular cell apoptosis and cidofovir-induced acute renal failure. 10926167 - Cellular and molecular mediators in common pathway mechanisms of chronic renal disease ... 9045927 - Immune modulation with interleukin-4 and interleukin-10 prevents crescent formation and... 15128887 - Histopathology of humorally mediated anti-glomerular basement membrane (gbm) glomerulon... 16393327 - Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following... 17155857 - Phosphodiesterase-4 inhibitors as a novel approach for the treatment of respiratory dis... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Arthritis and rheumatism Volume: 63 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-11-30 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
|
Languages: eng Pagination: 3897-907 Citation Subset: AIM; IM |
Copyright Information:
|
Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
|
University of Glasgow, Glasgow, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic...
Next Document: A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits ...