Skip to main content
Journal cover image

alpha(2)-Macroglobulin from rheumatoid arthritis synovial fluid: functional analysis defines a role for oxidation in inflammation.

Publication ,  Journal Article
Wu, SM; Pizzo, SV
Published in: Arch Biochem Biophys
July 1, 2001

A hallmark of inflammation is the release of oxidants, proteinases, and cytokines, all important mediators of the inflammatory cascade. alpha(2)-Macroglobulin (alpha(2)M) is a high-affinity, broad-specificity proteinase inhibitor that also binds and regulates the biological activities of a number of cytokines. We demonstrated recently that hypochlorite-oxidized alpha(2)M has decreased ability to inhibit proteinases and regulate cytokines in vitro. The role of oxidation in regulating alpha(2)M functions in vivo is largely unknown. To determine the extent and biological consequence of in vivo alpha(2)M oxidation, we measured the degree of oxidative alpha(2)M modification from rheumatoid arthritis (RA) synovial fluid and compared this with osteoarthritis (OA) as noninflammatory controls. We found that RA synovial fluid alpha(2)M is significantly more oxidized than that from OA. RA synovial fluid also contains a twofold higher median alpha(2)M level than OA, while having only half the alpha(2)M-proteinase inhibitory activity. Detailed biochemical analysis demonstrates proteolytically degraded alpha(2)M in RA greater than in OA synovial fluid. Additionally, the hypochlorite-mediated oxidation product, chlorotyrosine, is present in RA more than in OA or plasma alpha(2)M samples. Taken together, these findings confirm a role for oxidative regulation of inflammation by altering the functions of extracellular mediators such as alpha(2)M.

Duke Scholars

Published In

Arch Biochem Biophys

DOI

ISSN

0003-9861

Publication Date

July 1, 2001

Volume

391

Issue

1

Start / End Page

119 / 126

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Tyrosine
  • Synovial Fluid
  • Peptide Hydrolases
  • Oxidation-Reduction
  • Osteoarthritis
  • Mass Spectrometry
  • Hypochlorous Acid
  • Humans
  • Biochemistry & Molecular Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wu, S. M., & Pizzo, S. V. (2001). alpha(2)-Macroglobulin from rheumatoid arthritis synovial fluid: functional analysis defines a role for oxidation in inflammation. Arch Biochem Biophys, 391(1), 119–126. https://doi.org/10.1006/abbi.2001.2408
Wu, S. M., and S. V. Pizzo. “alpha(2)-Macroglobulin from rheumatoid arthritis synovial fluid: functional analysis defines a role for oxidation in inflammation.Arch Biochem Biophys 391, no. 1 (July 1, 2001): 119–26. https://doi.org/10.1006/abbi.2001.2408.
Wu, S. M., and S. V. Pizzo. “alpha(2)-Macroglobulin from rheumatoid arthritis synovial fluid: functional analysis defines a role for oxidation in inflammation.Arch Biochem Biophys, vol. 391, no. 1, July 2001, pp. 119–26. Pubmed, doi:10.1006/abbi.2001.2408.
Journal cover image

Published In

Arch Biochem Biophys

DOI

ISSN

0003-9861

Publication Date

July 1, 2001

Volume

391

Issue

1

Start / End Page

119 / 126

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Tyrosine
  • Synovial Fluid
  • Peptide Hydrolases
  • Oxidation-Reduction
  • Osteoarthritis
  • Mass Spectrometry
  • Hypochlorous Acid
  • Humans
  • Biochemistry & Molecular Biology