Development and validation of a mouse model of contemporary cannabis smoke exposure.

Autor:	Fantauzzi MF; Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Cass SP; Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., McGrath JJC; Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Thayaparan D; Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Wang P; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Stampfli MR; Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada., Hirota JA; Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada.
Jazyk:	angličtina
Zdroj:	ERJ open research [ERJ Open Res] 2021 Jul 19; Vol. 7 (3). Date of Electronic Publication: 2021 Jul 19 (Print Publication: 2021).
DOI:	10.1183/23120541.00107-2021
Abstrakt:	Cannabis is widely used for both recreational and medicinal purposes. Inhalation of combusted cannabis smoke is the most common mode of drug consumption, exposing the lungs to the pharmacologically active ingredients, including tetrahydrocannabinol (THC) and cannabidiol (CBD). While the relationship between cannabis smoke exposure and compromised respiratory health has yet to be sufficiently defined, previous investigations suggest that cannabis smoke may dysregulate pulmonary immunity. Presently, there exist few preclinical animal models that have been extensively validated for contemporary cannabis smoke exposure.  To address this need, we developed a mouse model with readouts of total particulate matter, serum cannabinoid and carboxyhaemoglobin levels, lung cellular responses, and immune-mediator production.  Using a commercially available smoke exposure system and a cannabis source material of documented THC/CBD composition, we exposed mice to a mean±sd total particulate matter of 698.89±66.09 µg·L -1 and demonstrate increases in serum cannabinoids and carboxyhaemoglobin. We demonstrate that cannabis smoke modulates immune cell populations and mediators in both male and female BALB/c mice. This modulation is highlighted by increases in airway and lung tissue macrophage populations, including tissue-resident alveolar macrophages, monocyte-derived alveolar macrophages, and interstitial macrophage subpopulations. No changes in airway or lung tissue infiltration of neutrophils were observed. Immune-mediator analysis indicated significant upregulation of macrophage-derived chemokine, thymus and activation-regulated chemokine, and vascular endothelial growth factor within the lung tissue of cannabis smoke-exposed mice.  This accessible and reproducible smoke-exposure model provides a foundation to explore the impact of chronic cannabis exposures and/or co-exposures with pathogens of clinical relevance, such as influenza. Competing Interests: Conflict of interest: M.F. Fantauzzi has nothing to disclose. Conflict of interest: S.P. Cass has nothing to disclose. Conflict of interest: J.J.C. McGrath has nothing to disclose. Conflict of interest: D. Thayaparan has nothing to disclose. Conflict of interest: P. Wang has nothing to disclose. Conflict of interest: M.R. Stampfli reports an employment opportunity pursued at CSL Behring outside the submitted work. Conflict of interest: J.A. Hirota is a cofounder of Infinotype, a startup company in the bioinformatics space, outside the submitted work. (Copyright ©The authors 2021.)
Databáze:	MEDLINE
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