title: Intradermal air pouch leukocytosis as an in vivo test for nanoparticles.
abstract: The need for test systems for nanoparticle biocompatibility, toxicity, and inflammatory or adaptive immunological responses is paramount. Nanoparticles should be free of microbiological and chemical contaminants, and devoid of toxicity. Nevertheless, in the absence of contamination, these particles may still induce undesired immunological effects in vivo, such as enhanced autoimmunity, hypersensitivity reactions, and fibrosis. Here we show that artificial particles of specific sizes affect immune cell recruitment as tested in a dermal air pouch model in mice. In addition, we demonstrate that the composition of nanoparticles may influence immune cell recruitment in vivo. Aside from biophysical characterizations in terms of hydrodynamic diameter, zeta potential, concentration, and atomic concentration of metals, we show that - after first-line in vitro assays - characterization of cellular and molecular effects by dermal air pouch analysis is straightforward and should be included in the quality control of nanoparticles. We demonstrate this for innate immunological effects such as neutrophil recruitment and the production of immune-modulating matrix metalloproteases such as MMP-9; we propose the use of air pouch leukocytosis analysis as a future standard assay.
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vandooren
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Berghmans
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Dillen
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Van Aelst
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ronsse
authors.affiliation: Department of Chemistry and Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel.
authors.forename: Liron Limor
authors.initials: LL
authors.lastname: Israel
authors.affiliation: Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Rosenberger
authors.affiliation: Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.affiliation: Department of Chemistry and Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Lellouche
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Michaeli
authors.affiliation: Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Locatelli
authors.affiliation: Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, Italy.
authors.forename: Mauro Comes
authors.initials: MC
authors.lastname: Franchini
authors.affiliation: New Materials Department, Fundación CIDETEC, San Sebastián, Spain.
authors.forename: Miren K
authors.initials: MK
authors.lastname: Aiertza
authors.affiliation: New Materials Department, Fundación CIDETEC, San Sebastián, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sánchez-Abella
authors.affiliation: New Materials Department, Fundación CIDETEC, San Sebastián, Spain.
authors.forename: Iraida
authors.initials: I
authors.lastname: Loinaz
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich, UK.
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Edwards
authors.affiliation: Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
authors.forename: Louis
authors.initials: L
authors.lastname: Shenkman
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000388:Air; D000818:Animals; D001681:Biological Assay / Q000295:instrumentation / Q000379:methods*; D007964:Leukocytosis / Q000139:chemically induced*; D008422:Materials Testing / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D011137:Polystyrenes; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods*
chemical_list: D011137:Polystyrenes
keywords: air pouch; biocompatibility; immunology; nanoparticles; toxicity