Document Detail


Alveolar macrophages from allergic lungs are not committed to a pro-allergic response and can reduce airway hyperresponsiveness following ex vivo culture.
MedLine Citation:
PMID:  18201249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We already demonstrated that adoptive transfer of alveolar macrophages (AMs) from non-allergic rats into AM-depleted allergic rats prevents airway hyperresponsiveness (AHR). We also showed that AMs from non-sensitized, but not from sensitized, allergy-prone rats can prevent AHR following allergen challenge in sensitized allergic animals, establishing the importance of rat immunological status on the modulation of AM functions and suggesting that an allergic lung environment alters AM functions. OBJECTIVE: We investigated how the activation of allergic AMs can be modulated to reinstitute them with their capacity to reduce AHR. METHODS: AMs from sensitized Brown Norway rats were cultured ex vivo for up to 18 h in culture media to deprogram them from the influence of the allergic lung before being reintroduced into the lung of AM-depleted sensitized recipient. AHR and cytokines in bronchoalveolar lavage (BAL) were measured following allergen challenge. AMs stimulated ex vivo with Bacillus Calmette-Guerin (BCG) were used as positive controls as BCG induces a T-helper type 1 activation in AMs. RESULTS: AMs ex vivo cultured for 4-18 h reduced AHR to normal level. Interestingly, pro-allergic functions of AMs were dampened by 18 h culture and they reduced AHR even after spending 48 h in an allergic lung microenvironment. Furthermore, transfer of cultured AMs caused an increase in the levels of IFN-gamma and IL-12 in BAL when compared with their ovalbumin control. After 18 h of ex vivo culture, AMs expressed reduced levels of TNF, IL-1alpha, IL-6, and Arginase-2 mRNAs compared with freshly isolated AMs, suggesting that ex vivo culture exempted AMs from lung stimuli that affected their functions. CONCLUSIONS: There is a significant crosstalk between lung microenvironment and AMs, affecting their functions. It is also the first report showing that sensitized AMs can be modulated ex vivo to reduce lung pro-allergic environment, opening the way to therapies targetting AMs.
Authors:
P Pouliot; A Spahr; E Careau; V Turmel; E Y Bissonnette
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-14
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  38     ISSN:  1365-2222     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-13     Completed Date:  2008-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  529-38     Citation Subset:  IM    
Affiliation:
Centre de recherche de l'Hôpital Laval, Institut universitaire de cardiologie et de pneumologie de l'Université Laval, Québec, QC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginase / genetics
Bronchial Hyperreactivity / physiopathology*
Bronchoalveolar Lavage Fluid / chemistry
Cell Separation
Cells, Cultured
Cytokines / analysis,  biosynthesis,  genetics
Hypersensitivity / immunology,  metabolism,  pathology*
Liposomes / pharmacology
Macrophages, Alveolar* / drug effects,  immunology,  pathology
Ovalbumin / immunology
RNA, Messenger / metabolism
Rats
Rats, Inbred BN
Time Factors
Chemical
Reg. No./Substance:
0/Cytokines; 0/Liposomes; 0/RNA, Messenger; 9006-59-1/Ovalbumin; EC 3.5.3.1/Arg2 protein, rat; EC 3.5.3.1/Arginase

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