Mobilizing the Rescue Squad

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Science  07 Sep 2001:
Vol. 293, Issue 5536, pp. 1731
DOI: 10.1126/science.293.5536.1731d

Certain cytokines such as G-CSF mobilizehematopoietic progenitor cells (HPCs), releasing them from the bone marrow. These cells can be collected from the blood of cytokine-treated leukemia patients before chemotherapy and reinfused after treatment to restore the patient's bone marrow. However, it is still not clear how cytokines elicit HPC mobilization.

Lévesque et al. report that G-CSF severs the connection between HPCs and the bone marrow stromal cells to which they are tethered. Apparently, G-CSF induces mouse bone marrow neutrophils to release two enzymes—neutrophil elastase and cathepsin G—which clip an adhesion molecule, VCAM1, from the surface of bone marrow stromal cells. VCAM1 binds to a β-integrin, VLA4, on the surface of HPCs, and thus cleavage of VCAM1 frees HPCs from their connection to the bone marrow stroma. Only bone marrow-derived neutrophils release proteases in response to cytokines. In patients before and after cytokine therapy, the increase in peripheral blood HPCs after treatment was mirrored by an increase in soluble VCAM1 in serum. Thus, G-CSF also promotes VCAM1 cleavage in humans, and this cleavage is directly related to HPC mobilization. — OMS

Blood98, 1289 (2001).

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