| Author | Morimoto, Konosuke | |
| Author | Janssen, William J | |
| Author | Fessler, Michael B | |
| Author | McPhillips, Kathleen A | |
| Author | Borges, Valéria de Matos | |
| Author | Bowler, Russell P | |
| Author | Xiao, Yi-Qun | |
| Author | Kench, Jennifer A | |
| Author | Henson, Peter M | |
| Access date | 2017-06-28T17:40:23Z | |
| Available date | 2017-06-28T17:40:23Z | |
| Document date | 2006 | |
| Citation | MORIMOTO, K. et al. Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease. Journal of Immunology, v. 176, p. 7657–7665, 2006. | pt_BR |
| ISSN | 0022-1767 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/19612 | |
| Description | Borges, Valéria de Matos “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. | pt_BR |
| Sponsorship | Atorvastatin Research Award (to R.W.V.) sponsored by Pfizer, COPD Center funding (to K.M.), Pew Latin American Fellows Program in the Biomedical Sciences (to V.M.B.), and by grants from the National Institutes of
Health to R.W.V. (HL072018) and P.M.H. (GM061031 and HL068864). | pt_BR |
| Language | eng | pt_BR |
| Publisher | American Association of Immunologists | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Lovastatina | pt_BR |
| Subject in Portuguese | Doença pulmonar obstrutiva crônica | pt_BR |
| Subject in Portuguese | Estatina | pt_BR |
| Subject in Portuguese | Inflamação | pt_BR |
| Title | Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease | pt_BR |
| Type | Article | pt_BR |
| Abstract | Statins are potent, cholesterol-lowering agents with newly appreciated, broad anti-inflammatory properties, largely based upon
their ability to block the prenylation of Rho GTPases, including RhoA. Because phagocytosis of apoptotic cells (efferocytosis) is
a pivotal regulator of inflammation, which is inhibited by RhoA, we sought to determine whether statins enhanced efferocytosis.
The effect of lovastatin on efferocytosis was investigated in primary human macrophages, in the murine lung, and in human
alveolar macrophages taken from patients with chronic obstructive pulmonary disease. In this study, we show that lovastatin
increased efferocytosis in vitro in an 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase-dependent manner. Lovastatin
acted by inhibiting both geranylgeranylation and farnesylation, and not by altering expression of key uptake receptors or
by increasing binding of apoptotic cells to phagocytes. Lovastatin appeared to exert its positive effect on efferocytosis by inhibiting
RhoA, because it 1) decreased membrane localization of RhoA, to a greater extent than Rac-1, and 2) prevented impaired
efferocytosis by lysophosphatidic acid, a potent inducer of RhoA. Finally, lovastatin increased efferocytosis in the naive murine
lung and ex vivo in chronic obstructive pulmonary disease alveolar macrophages in an HMG-CoA reductase-dependent manner.
These findings indicate that statins enhance efferocytosis in vitro and in vivo, and suggest that they may play an important
therapeutic role in diseases where efferocytosis is impaired and inflammation is dysregulated. | pt_BR |
| Affilliation | University of Colorado Health Sciences Center. Division of Pulmonary Sciences and Critical Care Medicine. Denver, Colorado / National Jewish Medical and Research Center. Department of Immunology. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Medicine. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Medicine. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Immunology. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Immunology. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Medicine. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Immunology. Denver, Colorado | pt_BR |
| Affilliation | National Jewish Medical and Research Center. Department of Immunology. Denver, Colorado | pt_BR |
| Affilliation | University of Colorado Health Sciences Center. Division of Pulmonary Sciences and Critical Care Medicine. Denver, Colorado / National Jewish Medical and Research Center. Department of Immunology. Denver, Colorado | pt_BR |
| Subject | Lovastatin | pt_BR |
| Subject | Chronic obstructive pulmonary disease | pt_BR |
| Subject | Statins | pt_BR |
| Subject | Inflammation | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
