PTX-sensitive signals in bone marrow homing of fetal and adult hematopoietic progenitor cells.
Several examples suggest a relationship between in vitro migratory capacity and bone marrow (BM) homing. Pertussis toxin (PTX) is a potent inhibitor of serpentine receptor-associated inhibitory trimeric guanidine nucleotide binding (Gi) protein signals. As such, it blocks hematopoietic progenitor cell migration in vitro, but contrary to expectation, no effects on BM homing were observed in previous studies. We therefore re-examined the effect of PTX on homing of murine BM and fetal liver (FL). We found that BM homing of PTX-incubated progenitor cells (colony-forming cells in culture [CFU-Cs]) from BM or FL in irradiated and nonirradiated recipients was reduced by more than 75%, with a concomitant increase in circulating CFU-Cs in peripheral blood. Additional studies confirmed the functional significance of this reduction in homing: PTX-treated cells did not provide radioprotection, and their short-term engraftment in BM and spleen was drastically reduced. Furthermore, several approaches show that cell-intrinsic rather than host-derived mechanisms are responsible for the PTX-induced homing defect. In summary, we show that Gi protein signals are required for BM homing and, as such, provide a new example of the association between BM homing and in vitro migration. Moreover, our data suggest that the behavior of hematopoietic progenitors in obeying Gi signaling does not diverge from that of mature leukocytes.
Bonig
Halvard
H
Department of Medicine, Division of Hematology, 1959 NE Pacific St, Box 357710, HSB-K257, Seattle, WA 98195-7710, USA.
Priestley
Gregory V
GV
Nilsson
Lina M
LM
Jiang
Yi
Y
Papayannopoulou
Thalia
T
D000199:Actins / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D005333:Fetus / Q000166:cytology / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012266:Ribose / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000199:Actins; D012266:Ribose; D037342:Pertussis Toxin; D019009:Proto-Oncogene Proteins c-kit; D019204:GTP-Binding Proteins