Blood, 1 October 2001, Vol. 98, No. 7, pp. 1999-2000
Eosinophil networking under the microscope
Hall and colleagues (page 2014) have succeeded in
applying a protein transduction approach to analyze the role of the
ras/ERK pathway in primary human eosinophils. This pathway has been
studied before in eosinophils with often equivocal results. In this
report Hall and colleagues have managed to transduce eosinophils with a
dominant-negative N17 H-Ras protein at very high efficiency. This has
allowed the authors to examine the outcome of several signaling
pathways and biologic activities of eosinophils stimulated with IL-5.
The results are quite compelling in that the ras/ERK pathway appears to
be selectively affected. Furthermore, the survival effect of IL-5 on
eosinophils is severely compromised, allowing the authors to offer a
strong, direct link between signaling and function.
Primary cells and, in particular, short-lived cells such as
eosinophils are notoriously difficult to transduce in a way that maintains their morphologic and functional integrity. The fact that
this can now be achieved offers the potential of inhibiting discrete
steps in the eosinophil signaling machinery to analyze functional
outcomes. The possibility therefore arises of establishing a
cause-and-effect link between signaling pathways and function. This
work should also encourage more work on primary eosinophils and less
emphasis on transduced cell lines, which often do not offer the same
range of functions or exhibit their own signaling machinery, which
makes extrapolation to the eosinophil rather risky. Given the role of
not only eosinophils but also myeloid cells in general in serious
inflammatory conditions such as asthma, there is the further potential
of clinically applying the protein transduction approach to selectively
inhibit myeloid cell function in vivo. Clearly reducing myeloid cell
survival would offer significant benefits in asthma. The proof of
principle has been established. The challenge remains of how best to
apply this approach to dissect signaling pathways and ultimately to
translate these findings into the clinical setting.
Angel Lopez
Hanson Centre for Cancer
Research
