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

Jonathan B. Rothbard, Michael P. Kurnellas, Sara Brownell, Chris M. Adams, Leon Su, Robert C. Axtell, Rong Chen, C. Garrison Fathman, William H. Robinson, Lawrence Steinman

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9708-9721
Number of pages14
JournalJournal of Biological Chemistry
Volume287
Issue number13
DOIs
StatePublished - Mar 23 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Rothbard, J. B., Kurnellas, M. P., Brownell, S., Adams, C. M., Su, L., Axtell, R. C., Chen, R., Fathman, C. G., Robinson, W. H., & Steinman, L. (2012). Therapeutic effects of systemic administration of chaperone αB-crystallin associated with binding proinflammatory plasma proteins. Journal of Biological Chemistry, 287(13), 9708-9721. https://doi.org/10.1074/jbc.M111.337691