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Secretion of macrophage urokinase plasminogen activator is dependent on proteoglycans

Gunnar Pejler1, Jan-Olof Winberg, Tram T Vuong

  • 1Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.

European Journal of Biochemistry
|September 27, 2003
PubMed

Insights

Proteoglycans are crucial for secreting urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) from macrophages. Inhibiting proteoglycan synthesis reduces the secretion of these key enzymes.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Proteoglycans play roles in cellular processes, including enzyme secretion.
  • Macrophage activation leads to the release of proteolytic enzymes.

Purpose of the Study:

  • To investigate the role of proteoglycans in the secretion of proteolytic enzymes, specifically urokinase plasminogen activator (uPA).
  • To examine the effect of inhibiting proteoglycan synthesis on enzyme secretion in macrophages.

Main Methods:

  • Murine macrophage cell line J774 were stimulated with phorbol ester (PMA).
  • Cells were treated with hexyl-beta-d-thioxyloside to inhibit proteoglycan synthesis.
  • Enzyme activity was measured using functional assays and zymography.
  • Protein levels were assessed by Western blotting, and mRNA levels by RT-PCR.

Main Results:

  • PMA stimulation increased urokinase plasminogen activator (uPA) secretion.
  • Xyloside treatment significantly reduced uPA activity and protein secretion in both unstimulated and PMA-stimulated macrophages.
  • The reduction in uPA was post-translational, as mRNA levels remained unchanged.
  • Xyloside treatment also decreased the secretion of matrix metalloproteinase 9 (MMP-9).

Conclusions:

  • Proteoglycans are essential for the efficient secretion of uPA and MMP-9 from macrophages.
  • The mechanism involves post-translational modification and secretion, not gene expression.
  • These findings highlight a novel regulatory role for proteoglycans in macrophage proteolytic activity.

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