TY - JOUR
T1 - Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model
AU - Crabbé, Aurélie
AU - Sarker, Shameema
AU - Van Houdt, Rob
AU - Ott, Mark
AU - Leys, Natalie
AU - Cornelis, Pierre
AU - Nickerson, Cheryl
A2 - Monsieurs, Pieter
N1 - Score = 10
PY - 2011/3
Y1 - 2011/3
N2 - The quorum sensing signal N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12 HSL), produced by Pseudomonas aeruginosa, exerts cytotoxic effects in macrophages in vitro, which is believed to affect host innate immunity in vivo. However,
the medical significance of this finding to pulmonary disease remains unclear since the multicellular complexity of the lung was not considered in the assessment of macrophage responses to 3-oxo-C12 HSL. We developed a novel threedimensional
co-culture model of alveolar epithelium and macrophages using the rotating wall
vessel (RWV) bioreactor, by adding undifferentiated monocytes to RWV-derived alveolar epithelium. Our three-dimensional model expressed important architectural/phenotypic hallmarks of the parental tissue, as evidenced by highly differentiated epithelium, spontaneous differentiation of monocytes to functional macrophage-like cells, localization of these cells on the alveolar surface and a macrophage-to-epithelial cell ratio relevant to the in vivo situation. Co-cultivation of macrophages with alveolar epithelium counteracted 3-oxo-C12 HSL-induced cytotoxicity via removal of quorum sensing molecules by alveolar cells. Furthermore,
3-oxo-C12 HSL induced the intercellular adhesion molecule ICAM-1 in both alveolar epithelium and macrophages. These data stress the importance of multicellular organotypic models to integrate the role of different cell types in overall
lung homeostasis and disease development in response to external factors.
AB - The quorum sensing signal N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12 HSL), produced by Pseudomonas aeruginosa, exerts cytotoxic effects in macrophages in vitro, which is believed to affect host innate immunity in vivo. However,
the medical significance of this finding to pulmonary disease remains unclear since the multicellular complexity of the lung was not considered in the assessment of macrophage responses to 3-oxo-C12 HSL. We developed a novel threedimensional
co-culture model of alveolar epithelium and macrophages using the rotating wall
vessel (RWV) bioreactor, by adding undifferentiated monocytes to RWV-derived alveolar epithelium. Our three-dimensional model expressed important architectural/phenotypic hallmarks of the parental tissue, as evidenced by highly differentiated epithelium, spontaneous differentiation of monocytes to functional macrophage-like cells, localization of these cells on the alveolar surface and a macrophage-to-epithelial cell ratio relevant to the in vivo situation. Co-cultivation of macrophages with alveolar epithelium counteracted 3-oxo-C12 HSL-induced cytotoxicity via removal of quorum sensing molecules by alveolar cells. Furthermore,
3-oxo-C12 HSL induced the intercellular adhesion molecule ICAM-1 in both alveolar epithelium and macrophages. These data stress the importance of multicellular organotypic models to integrate the role of different cell types in overall
lung homeostasis and disease development in response to external factors.
KW - Pseudomonas
KW - quorum sensing
KW - AHL
KW - RWV
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_112081
UR - http://knowledgecentre.sckcen.be/so2/bibref/7839
U2 - 10.1111/j.1462-5822.2010.01548.x
DO - 10.1111/j.1462-5822.2010.01548.x
M3 - Article
SN - 1462-5814
VL - 13
SP - 469
EP - 481
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 3
ER -