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

Research output: Contribution to journalArticle

Ewelina Hoffman, Aateka Patel, Doug Ball, Jan Klapwijk, Val Millar, Abhinav Kumar, Abigail Martin, Rhamiya Mahendran, Lea Ann Dailey, Ben Forbes, Victoria Hutter

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalPharmaceutical Research
Early online date24 May 2017
DOIs
Publication statusE-pub ahead of print - 24 May 2017

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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.

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