Platelet-derived growth factor BB-mediated normalization of dermal interstitial fluid pressure after mast cell

Asa Lidén1, Ansgar Berg, Torbjørn Nedrebø

  • 1Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden.

Circulation Research
|February 4, 2006
PubMed

Insights

Platelet-derived growth factor (PDGF)-BB normalizes interstitial fluid pressure during inflammation. This involves alphaVbeta3 integrin, which mediates tensile forces in connective tissue cells.

Area of Science:

  • Integrin biology
  • Connective tissue physiology
  • Inflammatory response

Background:

  • Interstitial fluid pressure (PIF) is crucial for regulating fluid balance in tissues.
  • Cell-mediated control of PIF is essential for maintaining normal tissue fluid content.
  • Beta1 integrins contribute to dermal PIF by mediating cellular tensile strength on the extracellular matrix.

Purpose of the Study:

  • To investigate the role of integrins in regulating interstitial fluid pressure during inflammatory responses.
  • To elucidate the mechanism by which platelet-derived growth factor-BB (PDGF-BB) normalizes PIF.
  • To identify the specific integrins involved in PDGF-BB-mediated PIF regulation.

Main Methods:

  • Utilized mouse models, including beta3-integrin-negative mice.
  • Administered anti-integrin antibodies (anti-beta1 and anti-beta3) and cyclic RGD peptides.
  • Assessed PIF changes following mast cell degranulation and anaphylaxis.
  • Evaluated collagen gel contraction by fibroblasts with varying integrin expression.

Main Results:

  • PDGF-BB normalized PIF reduced by anaphylaxis.
  • Anti-beta3 integrin antibodies and RGD peptides blocked PDGF-BB's ability to normalize PIF.
  • PDGF-BB failed to normalize PIF in beta3-negative mice.
  • Anti-beta1 integrin antibodies reduced PIF in normal dermis but did not affect PDGF-BB's normalization effect.
  • Collagen gel contraction was dependent on alphaVbeta3 integrin, particularly in the presence of PDGF-BB.

Conclusions:

  • AlphaVbeta3 integrin plays a critical role in controlling PIF during inflammatory reactions.
  • PDGF-BB stimulates connective tissue cells to generate tensile forces through alphaVbeta3 integrin during inflammation.
  • This study reveals a novel in vivo function for alphaVbeta3 integrin in regulating fluid dynamics during inflammation.