PTX-sensitive signals in bone marrow homing of fetal and adult hematopoietic progenitor cells.

Blood
Halvard BonigThalia Papayannopoulou

Abstract

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...Continue Reading

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Citations

Sep 7, 2012·Leukemia·H Bonig, T Papayannopoulou
Apr 2, 2008·The Journal of Experimental Medicine·Yuchun NieYong-Rui Zou
Oct 21, 2006·Current Opinion in Hematology·John P Chute
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Jan 7, 2019·Journal of Cell Communication and Signaling·Rodolfo Daniel Cervantes-VillagranaJosé Vázquez-Prado
Jul 3, 2021·Journal of Clinical Medicine·Deepak K SinghJulio A Aguirre-Ghiso

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