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Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
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Biomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte

Hannah Caitlin Cohen1, Dustin C Frost1, Tyler Jacob Lieberthal2

  • 1Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.

Biomaterials
|March 5, 2015
PubMed

Insights

Poly(ethylene glycol) hydrogels enhance polymorphonuclear neutrophil (PMN) primary granule release via adhesion, involving specific kinases. This discovery aids in directing biomaterial-induced inflammation for better wound healing.

Area of Science:

  • Biomaterials Science
  • Immunology
  • Wound Healing

Background:

  • The foreign body response involves polymorphonuclear neutrophils (PMNs) releasing granule subsets, influencing inflammation and healing.
  • Previous work showed PMNs on poly(ethylene glycol) (PEG) hydrogels exhibit enhanced primary granule release.
  • PMN primary granules contain proteins that can harm cells and degrade tissue, contributing to inflammation.

Purpose of the Study:

  • To elucidate the mechanism behind enhanced primary granule release from PMNs cultured on PEG hydrogels.
  • To investigate the role of adhesion, kinases, and adsorbed serum proteins in this process.

Main Methods:

  • Culturing PMNs on PEG-containing hydrogels and comparing them to controls.
  • Utilizing inhibitors for Src family kinases and PI3K-γ to assess their involvement.
  • Employing stable-isotope dimethyl labeling-based shotgun proteomics to identify adsorbed serum proteins.

Main Results:

  • Enhanced primary granule release from PMNs on PEG hydrogels is adhesion-mediated and dependent on Src family kinases and PI3K-γ.
  • Gelatin addition to PEG hydrogels did not further increase PMN primary granule release.
  • Proteomics identified increased adsorption of serum proteins, such as Ig gamma constant chain and alpha-1-acid glycoprotein 1, on PEG hydrogels.

Conclusions:

  • Adhesion to PEG hydrogels, mediated by specific kinases and influenced by adsorbed serum proteins, drives enhanced PMN primary granule release.
  • Understanding this mechanism allows for biomaterial design to modulate inflammatory responses for improved wound healing.
Keywords:
Acute inflammationDegranulationGelatinNeutrophilPoly(ethylene glycol)Protein adsorption

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