Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice.
Proc Natl Acad Sci U S A
; 99(9): 6228-33, 2002 Apr 30.
Article
en En
| MEDLINE
| ID: mdl-11983913
ABSTRACT
The CXC chemokine interleukin-8 (IL-8/CXCL8) induces rapid mobilization of hematopoietic progenitor cells (HPCs). Previously we showed that mobilization could be prevented completely in mice by pretreatment with neutralizing antibodies against the beta2-integrin LFA-1 (CD11a). In addition, murine HPCs do not express LFA-1, indicating that mobilization requires a population of accessory cells. Here we show that polymorphonuclear cells (PMNs) serve as key regulators in IL-8-induced HPC mobilization. The role of PMNs was studied in mice rendered neutropenic by administration of a single injection of antineutrophil antibodies. Absolute neutropenia was observed up to 3-5 days with a rebound neutrophilia at day 7. The IL-8-induced mobilizing capacity was reduced significantly during the neutropenic phase, reappeared with recurrence of the PMNs, and was increased proportionally during the neutrophilic phase. In neutropenic mice, the IL-8-induced mobilizing capacity was restored by the infusion of purified PMNs but not by infusion of mononuclear cells. Circulating metalloproteinase gelatinase B (MMP-9) levels were detectable only in neutropenic animals treated with PMNs in combination with IL-8, showing that in vivo activated PMNs are required for the restoration of mobilization. However, IL-8-induced mobilization was not affected in MMP-9-deficient mice, indicating that MMP-9 is not indispensable for mobilization. These data demonstrate that IL-8-induced mobilization of HPCs requires the in vivo activation of circulating PMNs.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Células Madre Hematopoyéticas
/
Interleucina-8
/
Neutrófilos
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2002
Tipo del documento:
Article
País de afiliación:
Países Bajos