Skip to main content

Oxidized α2-macroglobulin differentially regulates receptor binding by cytokines/growth factors

Publication ,  Journal Article
Wu, SM; Pizzo, SV
Published in: FASEB Journal
1998

α2-Macroglobulin (α2M) is a highly conserved, homotetrameric, broad-spectrum plasma and inflammatory fluid proteinase inhibitor that also binds to a wide variety of cytokines and growth factors such as TNF-α, IL-1β, IL-2, IL-6, IL-8, bFGF, βNGF, PDGF, and TGF-β1 and β2. Since many of these cytokines and growth factors are released during acute inflammation along with neutrophil-derived oxidants, we hypothesize that oxidation may alter the ability of α2M to bind to these cytokines/growth factors and result in differentially-regulated growth factor functions. Using sodium hypochlorite, a product of the neutrophil H2O2-myeloperoxidase-Cl- system, we show that oxidized α2M exhibits increased binding to TNF-α, IL-2, IL-6 and bFGF and decreased binding to βNGF, PDGF-BB, and TGF-β1 and β2. Hypochlorite oxidation of methylamine-treated α2M (α2M*), a synthetic analog of proteinase-α2M complex, results in either no change or decreased binding to the same growth factors. Using TGFβ as a model growth factor, we found that oxidized α2M and α2M* are both unable to inhibit TGFβ binding to cells and regulate TGFβ functions. In addition, we isolated α2M from human rheumatoid arthritis synovial fluid and showed that the protein is extensively oxidized and has significantly decreased ability to bind to TGF-β1. We, therefore, propose that oxidation serves as a switch mechanism which down-regulates the progression of acute inflammation by sequestering TNF-α, IL-2, and IL-6, while up-regulating the development of tissue-repair processes by releasing βNGF, PDGF, and TGFβ from binding to α2M.

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1998

Volume

12

Issue

4

Start / End Page

A485

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wu, S. M., and S. V. Pizzo. “Oxidized α2-macroglobulin differentially regulates receptor binding by cytokines/growth factors.” FASEB Journal 12, no. 4 (1998): A485.
Wu, S. M., and S. V. Pizzo. “Oxidized α2-macroglobulin differentially regulates receptor binding by cytokines/growth factors.” FASEB Journal, vol. 12, no. 4, 1998, p. A485.

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1998

Volume

12

Issue

4

Start / End Page

A485

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology