title: Expression of human carcinoembryonic antigen-related cell adhesion molecule 6 and alveolar progenitor cells in normal and injured lungs of transgenic mice.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is expressed in the epithelium of various primate tissues, including lung airway and alveoli. In human lung, CEACAM6 is developmentally and hormonally regulated, protects surfactant function, has anti-apoptotic activity and is dysregulated in cancers. We hypothesized that alveolar CEACAM6 expression increases in lung injury and promotes cell proliferation during repair. Studies were performed in CEABAC transgenic mice-containing human CEACAM genes. The level of CEACAM6 in adult CEABAC lung was comparable to that in human infants; expression occurred in epithelium of airways and of some alveoli but rarely co-localized with markers of type I or type II cells. Ten days after bleomycin instillation, both the number of CEACAM6(+) cells and immunostaining intensity were elevated in injured lung areas, and there was increased co-localization with type I and II cell markers. To specifically address type II cells, we crossed CEABAC mice with animals expressing EGFP driven by the SP-C promoter. After bleomycin injury, partially flattened, elongated epithelial cells were observed that expressed type I cell markers and were primarily either EGFP(+) or CEACAM6(+). In cell cycle studies, mitosis was greater in CEACAM6(+) non-type II cells versus CEACAM6(+)/EGFP(+) cells. CEACAM6 epithelial expression was also increased after hyperoxic exposure and LPS instillation, suggesting a generalized response to acute lung injuries. We conclude that CEACAM6 expression is comparable in human lung and the CEABAC mouse. CEACAM6 in this model appears to be a marker of a progenitor cell population that contributes to alveolar epithelial cell replenishment after lung injury.
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors.forename: Shin-E
authors.initials: SE
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Barrette
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chapin
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Linda W
authors.initials: LW
authors.lastname: Gonzales
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, California.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Gonzalez
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, California.
authors.forename: Leland G
authors.initials: LG
authors.lastname: Dobbs
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, California ballardp@peds.ucsf.edu.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Ballard
keywords: Alveolar epithelium; CEACAM6; lung injury; stem cells