Intravital microscopy imaging of macrophage localization to immunogenic particles and co-localized tissue oxygen saturation

Se Woon Choe, Abhinav P. Acharya, Benjamin G. Keselowsky, Brian S. Sorg

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Well-designed biomaterial polymer particle-based vaccines will optimally promote immune cell antigenpresenting behavior while minimizing adverse inflammatory responses to the particles and encapsulated drugs or adjuvants. It is important in the design of particle-based vaccines to consider possible harmful effects of immune response on tissue at the vaccination site. Intravital microscopy with rodent dorsal skin window chambers enables in vivo serial observations in the same animal, and such models which have been used to study angiogenesis and macrophage response to implanted biomaterials may also be useful for the development of particle-based vaccines. To our knowledge there have been no reports where intravital microscopy has documented real-time immune cell localization and potentially harmful co-localized tissue effects. In this proof-of-principle study we used fluorescence and spectral imaging intravital microscopy of mouse window chambers to measure macrophage localization and co-localized tissue microvessel hemoglobin saturation changes in response to an immunogenic stimulus from polymer particles loaded with lipopolysaccharide (LPS) serving as a model vaccine/adjuvant system. We observed greater and faster macrophage localization to stronger inflammatory stimuli from LPS-loaded particle doses, a trend of decreased microvessel oxygenation with increased macrophage accumulation and, in an extreme case, complete microvessel collapse accompanied by tissue necrosis. Our technique may be useful for optimizing design of particle-based vaccines and may give insight into the use of hemoglobin saturation as a biomarker of tissue inflammation for clinical investigations of particle-based vaccines.

Original languageEnglish (US)
Pages (from-to)3491-3498
Number of pages8
JournalActa Biomaterialia
Volume6
Issue number9
DOIs
StatePublished - Sep 2010
Externally publishedYes

Keywords

  • Image analysis
  • Immune response
  • In vivo test
  • Inflammation
  • Oxygen

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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