Correlating macrophage morphology and cytokine production resulting from biomaterial contact

J Biomed Mater Res A. 2013 Jan;101(1):203-12. doi: 10.1002/jbm.a.34309. Epub 2012 Jul 30.


The morphological and inflammatory responses of adherent macrophages are correlated to evaluate the biocompatibility of surfaces. Monocyte-derived macrophage (MDM), THP-1, and THP-1 cells expressing GFP-actin chimeric protein were seeded onto glass, polyurethane (PU), and glass surface modified with quaternary ammonium salt functionalized chitosan (CH-Q) and hyaluronic acid (HA). Using confocal microscopy, the surface area, volume and 3D shape factor of adherent macrophages was quantified. For comparison, functional consequences of cell-surface interactions that activate macrophages and thereby elicit secretion of a proinflammatory cytokine were evaluated. Using an enzyme linked immune sorbent assay, tumor necrosis factor-alpha (TNF-α) was measured. On glass, macrophages exhibited mainly an amoeboid shape, exhibited the largest surface area, volume, and 3D shape factor and produced the most TNF-α. On PU, macrophages displayed mainly a hemispherical shape, exhibited an intermediate volume, surface area and 3D shape factor, and produced moderate TNF-α. In contrast, on CH-Q and HA surfaces, macrophages were spherical, exhibited the smallest volume, surface area, and 3D shape factor, and produced the least TNF-α. These studies begin to validate the use of GFP-actin-modified MDM as a novel tool to correlate cell morphology with inflammatory cell response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Biocompatible Materials / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Shape / drug effects*
  • Cell Size / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Imaging, Three-Dimensional
  • Lentivirus / genetics
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Microscopy, Confocal
  • Monocytes / cytology
  • Recombinant Fusion Proteins / metabolism
  • Surface Properties
  • Transduction, Genetic
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / metabolism


  • Actins
  • Biocompatible Materials
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Green Fluorescent Proteins