Document Detail


Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model.
MedLine Citation:
PMID:  21054742     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The quorum sensing signal N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12) 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-C(12) HSL. We developed a novel three-dimensional 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-C(12) HSL-induced cytotoxicity via removal of quorum sensing molecules by alveolar cells. Furthermore, 3-oxo-C(12) 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.
Authors:
Aurélie Crabbé; Shameema F Sarker; Rob Van Houdt; C Mark Ott; Natalie Leys; Pierre Cornelis; Cheryl A Nickerson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-11-25
Journal Detail:
Title:  Cellular microbiology     Volume:  13     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  469-81     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Affiliation:
The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, 85287, USA. acrabbe@asu.edu
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
R21MH080702/MH/NIMH NIH HHS

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