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Innate immune modulation as a mechanism for therapeutic action of early EPCs in a nude rat model of pulmonary hypertension
Author(s) -
Ormiston Mark,
Deng Yupu,
Stewart Duncan J.,
Courtman David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.174.1
Subject(s) - cd86 , progenitor cell , medicine , cd14 , innate immune system , immune system , immunology , dendritic cell , transplantation , cancer research , pharmacology , stem cell , t cell , biology , microbiology and biotechnology
Early and late‐outgrowth endothelial progenitor cells (EPCs) were cultured from human leukapheresis samples and tested for therapeutic efficacy in a nude rat, monocrotaline (MCT)‐induced model of pulmonary hypertension (PH). Three days after injection of MCT, 10 6 cells were administered to nude rats via central venous injection. Three weeks after cell injection, right ventricular systolic pressure was elevated in MCT treated animals (61 ± 3.8 vs. 27 ± 0.5 mmHg no MCT control). The administration of early‐EPCs prevented the onset of PH (33 ± 3.2 mmHg), while delivery of late‐EPCs produced no improvement (60 ± 4.0 mmHg). Analysis of cell retention by histology and PCR revealed that, despite the therapeutic benefit of early‐EPCs, neither cell type was retained within the lung at 24 hours post injection. A subsequent in vitro characterization of early‐EPCs revealed a capacity to modulate the innate immune response in a manner similar to that of dendritic cells. Early‐EPCs, which are positive for CD14, MHC II, CD86 and CD11c, and negative for CD1a and CD83, increased surface expression of CD86 and CD83 and decreased surface CD14 in response to stimulation with LPS. Exposure to LPS also induced the secretion of IL‐10 but not IL‐12. As with dendritic cells, co‐culture of early‐EPCs with autologous natural killer (NK) cells in the presence of LPS induced NK cytotoxicity, suggesting a potential mechanism of therapeutic action.