Comparative lentiviral versus adenoviral gene transfer of GM-CSF to bone marrow-derived versus pulmonary macrophages of mice

Abstract

Granulocyte macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in the terminal differentiation and survival of alveolar macrophages with important implications for macrophage-dependent lung antibacterial immunity. We here assessed the transduction efficacy of murine bone marrow-derived monocytes (BMM) versus resident alveolar macrophages (rAM) employing either lentiviral or adenoviral vectors encoding for murine GM-CSF (LV-GM-CSF versus AdGM-CSF). Lentiviral transduction of BMM for 16 hours resulted in increased transgene and protein expression beginning at day 3 until day 28, with significantly improved survival of LV-GM-CSF as compared to LV-eGFP transduced BMM. In contrast, rAM demonstrated substantial cytotoxic cell death upon lentiviral transduction compared to BMM. In contrast, transfection of rAM with AdGM-CSF did not cause any cytotoxicity, and resulted in peak transgene and protein expression on day 7 post-transfection with a decline thereafter. These data reveal different efficacy profiles of viral vector systems in terms of transgene expression and cytotoxicity in pre-differentiated as compared to terminally differentiated macrophage populations.