Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice.
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.
Pruijt
Johannes F M
JF
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Verzaal
Perry
P
van Os
Ronald
R
de Kruijf
Evert-Jan F M
EJ
van Schie
Marianke L J
ML
Mantovani
Alberto
A
Vecchi
Annunciata
A
Lindley
Ivan J D
IJ
Willemze
Roel
R
Starckx
Sofie
S
Opdenakker
Ghislain
G
Fibbe
Willem E
WE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D011994:Recombinant Proteins; D020780:Matrix Metalloproteinase 9