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Selective and inducible targeting of CD11b+ mononuclear phagocytes in the murine lung with hCD68-rtTA transgenic systems

McCubbrey, AL;Barthel, L;Mould, KJ;Mohning, MP;Redente, EF;Janssen, WJ;

During homeostasis two distinct macrophage (M) populations inhabit the lungs: tissue M (often called interstitial M) and resident alveolar M (resAM). During acute lung inflammation, monocytes from the circulation migrate to areas of injury where they mature into a third M population: recruited M. Resident AM uniquely express low levels of CD11b and high levels of CD11c. In comparison, recruited M and tissue M express high levels of CD11b and low levels of CD11c. It is likely that these three M subpopulations play distinct roles in injury and disease states; however, tools with which to individually target or track these populations are lacking. Here we demonstrate the utility of an hCD68-rtTA transgenic system for specific, robust, and inducible targeting of CD11b(+) recruited M and tissue M in the murine lung with negligible activation in resAM. Using hCD68rtTA-GFP reporter mice, we show both during homeostasis and inflammation that administration of doxycycline induces tet-On reporter expression in recruited M and tissue M but not in resident AM. We further demonstrate how hCD68-rtTA can be effectively combined with tet-On Cre to target these same recM and tissue M. Accordingly, the hCD68-rtTA system is a powerful new tool that can be used for lineage tracing, fate mapping, and gene deletion in a variety of murine models, thereby enabling sophisticated investigation of the unique role of these CD11b(+) M during lung heath and disease.