Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters

<p>Abstract</p> <p>Background</p> <p>The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronc...

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Main Authors: Sutherland Mhairi, Shome Goutam, Wachtel Mitchell S, McGlone John J
Format: Article
Language:English
Published: BMC 2009-10-01
Series:BMC Immunology
Online Access:http://www.biomedcentral.com/1471-2172/10/58
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author Sutherland Mhairi
Shome Goutam
Wachtel Mitchell S
McGlone John J
author_facet Sutherland Mhairi
Shome Goutam
Wachtel Mitchell S
McGlone John J
author_sort Sutherland Mhairi
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure.</p> <p>Results</p> <p>The first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86).</p> <p>Conclusion</p> <p>A definition of murine histologic alterations resembling asthma in the BALB/c OVA mouse was developed and validated. The definition will be of use in experiments involving this model to ensure that all mice said to have undergone an asthmatic attack did indeed reveal allergic pulmonary inflammation. Proposed grading criteria should be further evaluated with additional studies using physiologic measures of attack severity and increased airway resistance.</p>
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spelling doaj.art-8b19c1d920bc4ce78f7338ea48095bf02022-12-21T21:04:35ZengBMCBMC Immunology1471-21722009-10-011015810.1186/1471-2172-10-58Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parametersSutherland MhairiShome GoutamWachtel Mitchell SMcGlone John J<p>Abstract</p> <p>Background</p> <p>The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure.</p> <p>Results</p> <p>The first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86).</p> <p>Conclusion</p> <p>A definition of murine histologic alterations resembling asthma in the BALB/c OVA mouse was developed and validated. The definition will be of use in experiments involving this model to ensure that all mice said to have undergone an asthmatic attack did indeed reveal allergic pulmonary inflammation. Proposed grading criteria should be further evaluated with additional studies using physiologic measures of attack severity and increased airway resistance.</p>http://www.biomedcentral.com/1471-2172/10/58
spellingShingle Sutherland Mhairi
Shome Goutam
Wachtel Mitchell S
McGlone John J
Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters
BMC Immunology
title Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters
title_full Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters
title_fullStr Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters
title_full_unstemmed Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters
title_short Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters
title_sort derivation and validation of murine histologic alterations resembling asthma with two proposed histologic grade parameters
url http://www.biomedcentral.com/1471-2172/10/58
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AT wachtelmitchells derivationandvalidationofmurinehistologicalterationsresemblingasthmawithtwoproposedhistologicgradeparameters
AT mcglonejohnj derivationandvalidationofmurinehistologicalterationsresemblingasthmawithtwoproposedhistologicgradeparameters