The role of metalloproteinases and adhesion molecules in interleukin-8-induced stem-cell mobilization.
The chemokine interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. Upon systemic injection, IL-8 induces an immediate neutropenia followed by a rebound granulocytosis. In this report, we discuss the effects of IL-8 on the mobilization of hematopoietic stem cells. Within 20 minutes following a single intraperitoneal injection in mice, IL-8 induces the mobilization of hematopoietic progenitor cells (HPC) with colony-forming, radioprotective, and long-term lymphomyeloid resubpopulating ability. Mobilization can be specifically prevented by pretreatment with antibodies against the beta2 integrin LFA-1 (CD11a). In monkeys, IL-8 Induces the rapid release of the metalloproteinase gelatinase-B concurrent with the mobilization of HPC. The latter effect can be prevented by blocking gelatinase-B activity using specific monoclonal antibodies, suggesting the involvement of gelatinase-B as a mediator of HPC mobilization. These results are consistent with the hypothesis that neutrophils are major regulators of stem-cell mobilization through the release of metalloproteinases (MMPs) that cleave extracellular matrix molecules to which HPC are attached.
Fibbe
W E
WE
Department of Hematology, Leiden University Medical Center, The Netherlands.
Pruijt
J F
JF
van Kooyk
Y
Y
Figdor
C G
CG
Opdenakker
G
G
Willemze
R
R
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000502:physiology*
D015815:Cell Adhesion Molecules; D016209:Interleukin-8; D020782:Matrix Metalloproteinases