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Diffuse Lung Disease |

Lovastatin Inhibits RhoA Expression and Increases Rac1/RhoA Ratio in Alveolar Macrophages

Kunihiko Hiraiwa, PhD; Stephan F. van Eeden, PhD
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UBC James Hogg Research Centre, Vancouver, BC, Canada


Chest. 2013;144(4_MeetingAbstracts):465A. doi:10.1378/chest.1702765
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Abstract

SESSION TITLE: Cytokines/Cellular Interactions Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM

PURPOSE: Statins are known to have immunomodulatory effects in addition to their lipid lowering properties. Previous in vivo studies from our laboratory have shown that statins promote the clearance of urban particulate matters from the lung in rabbits (Miyata et al. Chest 2012). The aim of this study is to evaluate the effect of statins on alveolar macrophages.

METHODS: We hypothesized that statins alter expression of receptors to recognize particulate matters and expression of molecules linked to phagocytosis and efferocytosis in alveolar macrophags. Lovastatin pretreated (n=11) and control (n=13) New Zealand White rabbits were euthanized and bronchoalveolar lavage were performed to isolate alveolar macrophages for immunohistochemical staining. Expression of scavenger receptor type A, toll-like receptor 4, and small GTPase (Rac1 and RhoA) was examined.

RESULTS: There was no significant difference in the expression of scavenger receptor type A, toll-like receptor 4, and Rac1 in the two groups. The fraction of alveolar macrophages stained positively for RhoA in the statin-treated group was 8.0 ± 4.1%, which was significantly lower than 44.3 ± 9.0% in the control group (p<0.01). The Rac-1/RhoA ratio in the treatment group was larger than the control group.

CONCLUSIONS: Rac1 and RhoA proteins are both involved in the regulation of efferocytosis; Rac1 enhances the process while RhoA inhibits it. The Rac1/RhoA ratio is important in efferocytic efficacy. Our study suggested that statin inhibited RhoA expression on alveolar macrophages while it had minimal impact on Rac1 expression. The increase of Rac1/RhoA ratio by statin treatment may augment efferocytosis ability of alveolar macrophages and contribute to immunomodulatory effects.

CLINICAL IMPLICATIONS: Exposure to toxic environmental particles is associated with lung and cardiovascular diseases. This study will reveal novel pathways to prevent the respiratory and cardiovascular adverse health effects in high-risk individuals expose to a polluted environment.

DISCLOSURE: The following authors have nothing to disclose: Kunihiko Hiraiwa, Stephan F. van Eeden

No Product/Research Disclosure Information


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