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J Biol Chem. 2012 Mar 23;287(13):9708-21. doi: 10.1074/jbc.M111.337691. Epub 2012 Feb 3.

Therapeutic effects of systemic administration of chaperone αB-crystallin associated with binding proinflammatory plasma proteins.

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1
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5316, USA.

Abstract

The therapeutic benefit of the small heat shock protein αB-crystallin (HspB5) in animal models of multiple sclerosis and ischemia is proposed to arise from its increased capacity to bind proinflammatory proteins at the elevated temperatures within inflammatory foci. By mass spectral analysis, a common set of ∼70 ligands was precipitated by HspB5 from plasma from patients with multiple sclerosis, rheumatoid arthritis, and amyloidosis and mice with experimental allergic encephalomyelitis. These proteins were distinguished from other precipitated molecules because they were enriched in the precipitate as compared with their plasma concentrations, and they exhibited temperature-dependent binding. More than half of these ligands were acute phase proteins or members of the complement or coagulation cascades. Consistent with this proposal, plasma levels of HspB5 were increased in patients with multiple sclerosis as compared with normal individuals. The combination of the thermal sensitivity of the HspB5 combined with the high local concentration of these ligands at the site of inflammation is proposed to explain the paradox of how a protein believed to exhibit nonspecific binding can bind with some relative apparent selectivity to proinflammatory proteins and thereby modulate inflammation.

PMID:
22308023
PMCID:
PMC3322989
DOI:
10.1074/jbc.M111.337691
[Indexed for MEDLINE]
Free PMC Article
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