Mechanisms underlying hematopoietic stem cell mobilization induced by the CXC chemokine interleukin-8.
The CXC chemokine interleukin-8 induces rapid mobilization of hematopoietic progenitor cells in mice and monkeys. Antibodies against the beta 2-integrin leukocyte function-associated antigen-1 completely blocked interleukin-8-induced mobilization. This was not due to a direct effect on the hematopoietic progenitor cells, as leukocyte function-associated antigen-1 was found not to be expressed on hematopoietic progenitor cells. Additional experiments showed that interleukin-8 induces the rapid release of the metalloproteinase gelatinase B, concurrent with the mobilization of hematopoietic progenitor cells. Mobilization could be completely prevented by anti-gelatinase B antibodies. Because neutrophils express leukocyte function-associated antigen-1 and high affinity interleukin-8 receptors, and release gelatinase B upon stimulation with interleukin-8, we hypothesized that neutrophils are key mediators in interleukin-8-induced stem cell mobilization. Further studies showed that mobilization by interleukin-8 was completely absent in mice rendered neutropenic with anti-granulocytic antibodies. Taken together, these data are consistent with an essential role for neutrophils in interleukin-8-induced stem cell mobilization.
Pruijt
J F
JF
Department of Hematology, Leiden University Medical Center, The Netherlands.
Willemze
R
R
Fibbe
W E
WE
D000818:Animals; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000502:physiology
D016209:Interleukin-8