title: Homing and conversion of murine hematopoietic stem cells to lung.
abstract: The hematopoietic stem cell population, lineage negative-Sca positive (HSC), displays a homing defect into bone marrow (BM) after 48-h exposure to interleukin (IL)-3, IL-6, IL-11, and steel factor [J. Hematother. Stem Cell Res. 11 (2002) 913]. Cytokine treatment of murine marrow leads to reversible alterations in adhesion protein expression, which may explain the changes in homing. We evaluated 3 h homing to nonhematopoietic organs of marrow cells exposed to cytokines for 0, 18, 24, 40 and 48 h. HSC cells from C57BL/6J mice were cultured and labeled with the cytoplasmic fluorescent dye CFSE. We found homed events from uncultured cells in spleen, liver and lung, but no events were seen in duodenum or anterior tibialis muscle. Culture in cytokines led to decreased homing to marrow at 24 and 48 h with parallel changes in spleen homing. There was little variability of homing to liver, however the number, of homed events in lung was markedly increased when 24-h cultured cells were assessed. This was approximately a 10-fold increase compared to the 0 h time point (flow cytometry). Homing was determined by evaluation of frozen section (8 microm) by fluorescent microscopy for spleen, liver, duodenum, anterior tibialis and lung. Data were confirmed by flow cytometry from each organ including marrow. These data indicate the presence of a lung homing "hotspot" at 24 h of cytokine culture; this is a time when the stem progenitors cells are in mid S-phase. Altogether these data suggest that homing of marrow cell to nonmarrow organs may fluctuate with cell cycle transit and that there is a lung homing hotspot in mid-S.
authors.affiliation: Department of Research and Medicine and the Decof Cancer Center, Roger Williams Medical Center, Providence, RI 029908-4735, USA. mdooner@rwmc.org
authors.forename: Mark
authors.initials: M
authors.lastname: Dooner
authors.forename: Jan
authors.initials: J
authors.lastname: Cerny
authors.forename: Gerald
authors.initials: G
authors.lastname: Colvin
authors.forename: Delia
authors.initials: D
authors.lastname: Demers
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pimentel
authors.forename: Deborah
authors.initials: D
authors.lastname: Greer
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Abedi
authors.forename: Christina
authors.initials: C
authors.lastname: McAuliffe
authors.forename: Peter
authors.initials: P
authors.lastname: Quesenberry
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D008168:Lung / Q000166:cytology; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology