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Innate immunity in the therapeutic actions of endothelial progenitor cells in pulmonary hypertension.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2010 Nov; Vol. 43 (5), pp. 546-54. Date of Electronic Publication: 2009 Dec 07. - Publication Year :
- 2010
-
Abstract
- Direct injection of endothelial progenitor cells (EPCs) into the circulation has shown therapeutic benefit in both experimental models and clinical studies of pulmonary arterial hypertension (PAH). Using the monocrotaline (MCT)-induced rat model of PAH, we investigated the role of innate immunity in the therapeutic activity of two types of putative EPCs derived from human peripheral blood mononuclear cells: an early population of endothelial-like, culture-modified monocytes (E-CMMs) and late-outgrowth EPCs (L-EPCs), which exhibit a strong endothelial phenotype. In the athymic nude rat, E-CMMs prevented MCT-induced increases in right ventricular systolic pressure (P < 0.001) and right ventricular hypertrophy (P < 0.01) when administered 3 days after MCT challenge, whereas L-EPCs were ineffective. However, in both cases, there was a lack of cell persistence within the lungs at 24 hours after injection, likely due to residual natural killer (NK) cell activity in the model. Although ablation of NK and NK-T cells with anti-asialo-GM-1 antiserum enhanced the retention of both E-CMMs and L-EPCs, still no benefit was seen with L-EPCs, and the efficacy of E-CMMs was lost. In vitro characterization revealed that E-CMMs resemble a regulatory subtype of dendritic cells, producing IL-10, but not IL-12, in response to inflammatory stimuli. Coculture studies demonstrated the capacity of E-EPCs to stimulate autologous human and nude rat NK cells in vitro. These data support a novel mode of action for human E-CMMs in the prevention of PAH, whereby they act through an immune-dependent mechanism, potentially involving the stimulation of NK cells.
- Subjects :
- Animals
Biomarkers metabolism
Blood Pressure
Cell Death
Cells, Cultured
Coculture Techniques
Dendritic Cells cytology
Dendritic Cells immunology
Disease Models, Animal
Flow Cytometry
Humans
Hypertension, Pulmonary physiopathology
Killer Cells, Natural cytology
Killer Cells, Natural immunology
Lung immunology
Lung pathology
Lung physiopathology
Monocrotaline
Monocytes cytology
Monocytes immunology
Rats
Rats, Nude
Spleen cytology
Endothelial Cells cytology
Endothelial Cells immunology
Hypertension, Pulmonary immunology
Hypertension, Pulmonary therapy
Immunity, Innate immunology
Stem Cells cytology
Stem Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4989
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 19995942
- Full Text :
- https://doi.org/10.1165/rcmb.2009-0152OC