Blood, 1 December 2001, Vol. 98, No. 12, pp. 3178-3178
Regulation of granulopoiesis: lessons from leukocyte
adhesion deficiency
The mechanisms that regulate granulopoiesis, in
particular, stress (or "emergency") granulopoiesis, are
incompletely understood. Studies of granulocyte colony-stimulating
factor (G-CSF) or G-CSF receptor-deficient mice provide strong
evidence that G-CSF is the principal hematopoietic cytokine regulating
basal granulopoiesis. But there is evidence that stress granulopoiesis
may be regulated in both a G-CSF-dependent and -independent fashion.
For example, in G-CSF-deficient mice, the neutrophil
response to infection with Listeria monocytogenes is
impaired (Lieschke et al, Blood. 1994;84:1737-1746), whereas it is
normal after challenge with Candida albicans (Basu et al,
Blood. 2000;95:3725-3733). In any event, the signals that regulate the
release of G-CSF or other granulopoietic cytokines are poorly characterized.
Forlow and colleagues (page 3309) examine the mechanisms
responsible for the neutrophilia associated with CD18 (
2-integrin) deficiency. Based on their data and data generated by Horwitz and
colleagues using a similar strategy (Blood. 2001;97:1578-1583), the
authors suggest the novel hypothesis that granulopoiesis may be
regulated through a feedback loop sensing neutrophil accumulation in
peripheral tissues. Moreover, evidence is provided suggesting that
IL-17, through stimulation of G-CSF release, is driving granulopoiesis in CD18-deficient mice. These provocative findings raise several important questions. Because CD18 deficiency results in a marked susceptibility to infection, what role, if any, do subclinical infections play in driving granulopoiesis in these mice? What cell type
or types are responsible for the production of IL-17 in this pathway,
and how do they sense the number of neutrophils present in tissues?
Clearly, there are IL-17- and G-CSF-independent pathways regulating granulopoiesis; what are the components of these pathways, and how are they regulated? The present study suggests
an exciting new avenue of granulopoiesis research, one that eventually
may lead to novel strategies to modulate neutrophil production.
Daniel C. Link
Washington University School of Medicine
