title: Selective and inducible targeting of CD11b+ mononuclear phagocytes in the murine lung with hCD68-rtTA transgenic systems.
abstract: During homeostasis two distinct macrophage (Mø) populations inhabit the lungs: tissue Mø (often called interstitial Mø) and resident alveolar Mø (resAMø). During acute lung inflammation, monocytes from the circulation migrate to areas of injury where they mature into a third Mø population: recruited Mø. Resident AMø uniquely express low levels of CD11b and high levels of CD11c. In comparison, recruited Mø and tissue Mø express high levels of CD11b and low levels of CD11c. It is likely that these three Mø 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 Mø and tissue Mø in the murine lung with negligible activation in resAMø. Using hCD68rtTA-GFP reporter mice, we show both during homeostasis and inflammation that administration of doxycycline induces tet-On reporter expression in recruited Mø and tissue Mø but not in resident AMø. We further demonstrate how hCD68-rtTA can be effectively combined with tet-On Cre to target these same recMø and tissue Mø. 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(+) Mø during lung heath and disease.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado; mccubbreya@njhealth.org.
authors.forename: Alexandra L
authors.identifier: 0000-0002-2049-9609
authors.initials: AL
authors.lastname: McCubbrey
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado;
authors.forename: Lea
authors.initials: L
authors.lastname: Barthel
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado; Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Mould
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado; Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mohning
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado; Department of Research, Denver Veterans Affairs Medical Center, Denver, Colorado.
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Redente
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado; Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: William J
authors.initials: WJ
authors.lastname: Janssen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D039481:CD11b Antigen / Q000378:metabolism*; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D010586:Phagocytes / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D008070:Lipopolysaccharides; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: CD11b+ macrophages; hCD68-rtTA; mouse model; recruited macrophages; transgenic mice