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Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis. / Hoffman, Ewelina; Bodhaniya, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben ; Hutter, Victoria.

In: Pharmaceutical Research, Vol. 34, No. 12, 31.12.2017, p. 2466-2476.

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Hoffman, Ewelina ; Bodhaniya, Aateka ; Ball, Doug ; Klapwijk, Jan ; Millar, Val ; Kumar, Abhinav ; Martin, Abigail ; Mahendran, Rhamiya ; Dailey, Lea Ann ; Forbes, Ben ; Hutter, Victoria. / Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis. In: Pharmaceutical Research. 2017 ; Vol. 34, No. 12. pp. 2466-2476.

Bibtex

@article{16b0343729a3425baa242b6e4f06fad8,
title = "Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis",
abstract = "Purpose. Progress to the clinic may be delayed or prevented when vacuolated or “foamy” alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures.Methods. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Results. Cell health, morphology and lipid content were comparable (p<0.05) for both cell lines and the primary macrophages in terms of vacuole number, size and lipid content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed.Conclusions. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.",
keywords = "foamy macrophage, NR8383, U937, toxicology, vacuolation",
author = "Ewelina Hoffman and Aateka Bodhaniya and Doug Ball and Jan Klapwijk and Val Millar and Abhinav Kumar and Abigail Martin and Rhamiya Mahendran and Dailey, {Lea Ann} and Ben Forbes and Victoria Hutter",
note = "{\circledC} The Author(s) 2017. This article is an open access publication. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.",
year = "2017",
month = "12",
day = "31",
doi = "10.1007/s11095-017-2176-5",
language = "English",
volume = "34",
pages = "2466--2476",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "12",

}

RIS

TY - JOUR

T1 - Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis

AU - Hoffman, Ewelina

AU - Bodhaniya, Aateka

AU - Ball, Doug

AU - Klapwijk, Jan

AU - Millar, Val

AU - Kumar, Abhinav

AU - Martin, Abigail

AU - Mahendran, Rhamiya

AU - Dailey, Lea Ann

AU - Forbes, Ben

AU - Hutter, Victoria

N1 - © The Author(s) 2017. This article is an open access publication. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

PY - 2017/12/31

Y1 - 2017/12/31

N2 - Purpose. Progress to the clinic may be delayed or prevented when vacuolated or “foamy” alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures.Methods. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Results. Cell health, morphology and lipid content were comparable (p<0.05) for both cell lines and the primary macrophages in terms of vacuole number, size and lipid content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed.Conclusions. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

AB - Purpose. Progress to the clinic may be delayed or prevented when vacuolated or “foamy” alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures.Methods. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Results. Cell health, morphology and lipid content were comparable (p<0.05) for both cell lines and the primary macrophages in terms of vacuole number, size and lipid content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed.Conclusions. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

KW - foamy macrophage

KW - NR8383

KW - U937

KW - toxicology

KW - vacuolation

U2 - 10.1007/s11095-017-2176-5

DO - 10.1007/s11095-017-2176-5

M3 - Article

VL - 34

SP - 2466

EP - 2476

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 12

ER -